SARS-CoV-2 sequencing and analysis in late Dec 19
Post 1: Weixin post by 小山狗 (Little Mountain Dog), on the 28th Jan 2020
Using screenshots (some with blurred sections)
of her WeChat conversation with colleagues from end Dec 19
小山狗 = Xiǎoshān Gǒu, a nickname for an employee of Vision Medicals (微远基因)
links for the post:
original page deleted by author
archived post, pdf version,weibo copy,
archived Weixin search showing multiple copies (29 Mar 22)
compare with censored latest Weixin search
Winjor 小山狗 2020-01-30
探索版的分析结果提示这个病原体跟Bat SARS like coronavirus最相似
Recording the experience of being the first to discover the
Winjor Little Mountain Dog 2020-01-30
I just started work on December 26, 2019, and as usual, I first roughly
browsed through the mNGS pathogenic microorganism auto-read
results for the day. If there is no problem, I will start the R&D work for
Unexpectedly, I found that one sample reported a sensitive pathogen -
SARS coronavirus, with dozens of sequences, and this sample only
has such a meaningful pathogen. If it is a common virus, this is already
a fairly reliable result. Feeling nervous, I quickly checked the detailed
analysis data in the background, and found that the similarity is not
very high, only about 94.5% (this is related to the similarity threshold,
which is equivalent to only screening out sequences with relatively high
Several possibilities come to mind: 1. There are certain differences in
the genomes of different strains of SARS; 2. RNA viruses are easy to
mutate, and it has been 17 years since the SARS event, and the
mutation is relatively large; 3. The wrong alignment of closely related
To confirm the reliability of the results, a detailed analysis was started.
Fortunately, I have encountered this kind of similar sensitive pathogen
confirmation analysis several times before, and the leader has
discussed with me several times whether it is possible to do an
analysis process for automatic discovery of new pathogens in the
samples, and I have always kept this in mind. While working on other
projects with higher weight and higher priority, I made a preliminary
version of [the analysis process], and this sample can just come in
I gave a name [to that process]. Compared with the analysis process
used in daily production, that process has an additional suffix:
"Exploration Edition", which contains almost all sequenced viral
The analysis results of that Exploratory Edition suggest that this
pathogen is most similar to Bat SARS like coronavirus, with an overall
similarity of about 87%, and a similarity to SARS of about 81%. The
number of sequences in the alignment has increased from dozens to
more than 500 [in that exploratory process]. In addition, 5 contigs have
been assembled, which add up to more than 1200 bp. At this time, it
can basically be confirmed that it is a coronavirus, and the detailed
analysis of the coronavirus can be carried out. During the analysis, we
also started a small internal confidential discussion with the head and
leader of the interpretation team.
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.1/54
列去blastn，结果都是跟Bat SARS like coronavirus最相似，但整体的相
并没有去调研过Bat SARS like 跟SARS的分类方法，在NCBI
Taxonomy上，Bat SARS like 是划分到SARS下面的
因组的相似度，潜意识里认为既然Bat SARS like是SARS的下属分类，
那么这个检测到的未知病毒至少也是一个跟Bat SARS like平行的物种
，即一个新型的Bat SARS like（后来看文献SARS和Bat SARS like是通
December 26, 2019 at 09:28 am
SARS all came out here1
My god, which sample is this
It’s no joke
It’s the same level as the plague
Further analysis, whether the original sequence is used as a query
sequence for blastn to NCBI nt library, or the assembled sequence is
used for blastn, the results are the most similar to Bat SARS like
coronavirus, but the overall similarity is only about 87%. When blastx
against the nr library protein is performed, the comparison returns
about the same similarity, so the results remain fuzzy.
Are bat coronaviruses as infectious as
. This sample you handle it separately
OK, i'm analysing
SARS itself came from bats
And civet cats
December 26, 2019 at 10:24 am
.. that’s the final identification
December 26, 2019 10:25 am
Taxonomically a subtype of SARS
The classification information of viruses has always been confusing,
and the classification rules are not uniform. Some are based on typing
genes (such as influenza A), and some have no clear typing genes,
and are classified by other methods. I have not investigated the
classification method of Bat SARS like and SARS before. On NCBI
Taxonomy, Bat SARS like is classified under SARS.
In such an urgent situation, there is no time to research the literature,
and there is not much data in hand. Based on the similarity of the
genome, I subconsciously think that since Bat SARS like is a
subordinate classification of SARS, then this detected unknown virus is
at least a related virus. Bat SARS-like parallel species, that is, a new
type of Bat SARS like (later I saw in the literature that SARS and Bat
SARS-like are classified by several non-structural proteins).
1Little Mountain dog WeChat messages are in green on the right. The messages of the person she is talking to at the time are against a white background on
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (firstname.lastname@example.org), p.2/54
We further did a very very broad comparison of the virus to thousands
of coronavirus genomes, which we evaluated in terms of similarity,
coverage, and even genome distribution, and finally found the two most
similar genomes, bat-SL-CoVZC45 and bat-SL-CoVZXC21 (After the
genome sequence was released on January 9, many articles analysed
(The picture was sent to the group in the afternoon)
December 26, 2019 14:42 pm
Now the information analysis can confirm that it
is SARS virus, but it is not clear whether it is a
December 26, 2019 15:01 pm
From the sequence number and coverage map,
it is the best fit for Bat_SARS_like_coronavirus
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This information alone is not enough, at least we have to look at the
evolutionary information, so I started to do a phylogenetic tree analysis.
December 26, 2019 10:25 am
Taxonomically a subtype of SARS
Can you make a phylogeny tree, plus
coronavirus, SARS, MERS from humans,
fruit bats and several other mammals
I'm looking for genomes to do this
Too many categories, hard to find
Downloaded the genomes of all coronaviruses, and finally 160
coronavirus genes (basically including all known coronaviruses of
various animals) were kept after quality filtering, clustering and other
analysis. The assembled sequence and 160 coronavirus genomes
were analysed based on the average similarity of the whole genome.
(As an aside, I personally think that in the analysis of species evolution,
it is more accurate and reasonable to construct an evolutionary tree
based on the average similarity of the whole genome than one based
on a certain gene. After all, it is considered from a global perspective.
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结果不出意外，还是跟Bat SARS like coronavirus聚得最近，而且也是
In addition, the assembled sequence was also very short at that time
[26th Dec], and there was no complete gene sequence.)
The result is not unexpected, it is still close to Bat SARS like
coronavirus, and it is also on the big branch of SARS.
(Picture in the evening)
WHO-specific PCR target genes detected
December 26, 2019 17:23 pm
WHO-specific PCR target genes
have no comparison
Evolutionary tree analysis: contains too
December 26, 2019 17:26 pm
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like，再往外的大蓝边是另一群Bat SARS like，未知的病毒跟45、21聚
Legend: A large red block in the upper left corner is SARS, the edge
colour that is not so red is for Bat SARS like, and the big blue border
outside is another group of Bat SARS like, the unknown virus is
clustered with 45 and 21 in a relatively independent branch up there,
the red frame is circled.
It is strange that this unknown virus clustered with bat-SL-CoVZC45
and bat-SL-CoVZXC21 in a relatively independent branch, while other
Bat SARS-like viruses were clustered in the SARS group.
I thought that maybe there is a problem with the classification of these
two. However, after reading the literature, there is no difference
between the method and the others, so I respect the classification of
the literature and I think that it is correct for the time being. (This is also
one of the bases for some experts to later consider this unknown virus
as a novel coronavirus)
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(Partial evolution tree screenshot)
The front-end feedback was that the patient is seriously ill. The test
results are urgently needed, but such a major pathogen cannot be
easily reported. I had an emergency meeting with several leaders at
noon and decided to continue the in-depth analysis, delay the release
of the report, while sharing the data to the Institute of Pathogen Biology
of the Chinese Academy of Medical Sciences so that they can get a
piece of the analysis.
Later in-depth analysis was carried out at the gene level (orf1ab, S, N
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.7/54
and other genes), and there was no significant discovery, mainly
because the number of detected sequences was small, the coverage
rate was too low, and they were all incomplete genes to do anything.
December 26th, 2019 at 23:22 pm
The level of expression of different genes
will vary, right?
December 26, 2019 at 23:30 pm
I just found the strain with the highest
similarity, the S region is 21,483~25,220, our
sequencing data still matched more than 30
accessions [strains] , but they are all in
the tail region after 24,000
Retesting of complementary data for analysis was proposed at noon.
Retesting can be used to verify technical reproducibility, avoid false
positives due to contamination by some unknown factors, and ensure
that the sample does contain the pathogen. In addition, more data can
be analysed. For example, if a complete genome can be assembled,
the analysis results are more reliable, and more in-depth analysis can
December 26, 2019, 12:09 noon
[blurred] Can the method be enriched?
See if you can assemble a more complete
Looks a bit like a new type
The next day (2019.12.27), after the data came out early in the
morning, the assembly analysis was carried out quickly, and a nearly
complete genome sequence was finally assembled.
The data was also shared, with the Institute of Pathogen Biology of the
Chinese Academy of Medical Sciences, for other in-depth analyses.
This time, the number of sequences has increased from more than 500
to more than 470,000!
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Because of time constraints and other R&D projects, we did not go into
detail to fill in the gaps in the assembly results to obtain the complete
genome. In addition, we have already shared the data with the Institute
of Pathogen Biology [of the Chinese Academy of Medical Sciences],
and they will also do that, so we did not assemble a complete genome
sequence, and the existing assembly results can meet most of the
Some in-depth analysis is also continued later.
The sequence distribution of the repeats is even, there is no obvious
preference, the average depth and median depth are basically the
same, and the depth reaches 1000x, indicating that there is no problem
with the assembly and that the sequencing is also rather good, and that
the unknown pathogen also has a complete genome.
December 27, 2019 at 10:19 am
Take the raw data and compare the overlay graph
of the coverage map
December 27, 2019 at 10:36 am
[blurred] Is updating the evolution tree time
It's alright if you leave out some species
I was able to match some of the oriented regions,
but there were some mismatches.
The similarity is also around 90%, on par with the
The evolutionary tree was constructed again. This time, the reference
strains of all coronaviruses in NCBI were selected (the accession
number starts with NC, which is officially considered the most credible),
plus a few strains from the most recent source analysed the day
before. [image in black is the detailed tree]
The evolutionary tree results are basically the same as the previous
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.9/54
SARS like coronavirus类似的新型病毒。
Genome collinearity analysis, ORF annotation, etc. indicate that this
unknown coronavirus is a typical BetaCoV (orf1ab, S, M, N, E, etc.
genes). The lighter colour in the collinearity map is the S protein region,
which is the gene with the greatest difference.
After adjusting the order of our assembly results, it is
basically consistent with the genome structure of
After comparing with the 7 PCR-verified target sequences of SARS
recommended by the WHO official website, it was found that the
average similarity was only about 90%. The key is that the primer
sequences also have several variations. It is speculated that the SARS
detection kit cannot detect this unknown pathogen (This was also true
for many of the later local experimental validations).
In addition, many other detailed in-depth analyses of genes and
proteins were carried out, which will not be repeated here.
At this point in the analysis, it was basically confirmed that there was
indeed a virus in this patient's sample, but this virus was not very
similar to all viruses with known genomic information, and may be a
new virus similar to Bat SARS like coronavirus
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Is it possible to issue a case, is the doctor
willing to issue a case?
[blurred, name?] it's not about the case
This is worse than the plague
The sequences currently covered by [blurred
BA] do two alignments:
1. structural protein regions;
2. targeting regions of the WHO seven pairs
It's not good, another serious public health
If so, we may also need to give the alert,
isolate, and prevent human-to-human
transmission as soon as possible.
and the laboratory
(Looking back at what I said at the time, it was a prophecy. I'm sorry for
the people of the whole country. Blame me for jinxing it2.)
This is not necessarily SARS, the infectivity and pathogenicity are
unknown, and at the same time, aware of the potential seriousness of
the problem, the laboratory3has been thoroughly cleaned and
disinfected, the samples were harmlessly destroyed, and the relevant
personnel involved in the experimental operation went through the
The next step is how to report the problem. Reporting directly may
scare the doctor, not to mention that this may be a new virus, and a
wrong report will be a major accident. Some necessary information still
needs to be checked first.
The first thing that comes to mind is, of course, the history of contact
with wild animals. At that time, the information was that the patient had
returned to his hometown, and it was not ruled out that he had come
into contact with bats or was bitten by bats.
December 27, 2019 14:05 pm
Do you have information on living, working
environment, and field exposure history?
Returned home before falling ill
3Meaning the Vision Medicals laboratory where that SARS-CoV-2 sample was handled.
2The Chinese idiom is ‘blame me for my crow’s mouth’ (都怪我这 个乌鸦嘴).
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SARS，想着或者仅仅只是个野生的Bat SARS like，传染性未知，所以
It was also suspected that some staff working somewhere4with
man-made viruses may have been infected by accident because
of careless handling. After all, the outbreak of Brucellosis some time
ago was caused by incomplete sterilisation of the bacteria at a certain
December 27, 2019 at 09:54 am
Yesterday I saw that the teacher [name? blurred]
said that the Wuhan Institute of Virology is located
Then Brucella was produced by the upstream
vaccine manufacturer without sterilising the aerosol
If there is no more information, it is still necessary to communicate this
matter with the doctor quickly. After all, we can guarantee that the
sample sent for inspection contains this unknown virus, and other
matters will be handed over to the doctor to investigate and deal with.
Information has been shared with the doctor before noon, and the
patient has also been isolated.
What is the decision now? Have you
communicated with the doctor?
Coronavirus is communicated, the patient is in
very serious condition, quarantine measures are
December 27, 2019 at 13:47 am
Because there is no other information, the patient is also isolated, and
this virus is not a real SARS. I think that it is just a wild Bat SARS like,
and the infectivity is unknown, so my nervousness is somewhat
relaxed. However, because the patient is seriously ill, it should not be
underestimated, and we are still in close communication with the
hospital. During that period, we continue to do some in-depth analysis.
On the 27th and 28th, the leaders of the company also
communicated with the hospital and the CDC people by telephone
on that matter. On the 29th and 30th, they also went to Wuhan in
person to report and exchange this matter with the leaders of the
hospital and the CDC, including all our analysis results and the
analysis results of the Institute of Pathogen Biology of the
Academy of Medical Sciences.
Everything was under intense, confidential, and rigorous
investigation (at this time, the hospital and CDC people already knew
that there were many similar patients, and after we communicated the
test results, emergency treatment was started, but I didn't know it).
I thought that this matter would pass soon. After all, apart from this
patient, it seems that no other patients have been infected. However,
by December 30, I heard that there are quite a few patients with similar
Suddenly I was again tense. In particular, about the afternoon of the
30th,a "friend business" may have detected the same virus in
another patient's sample, but they directly sent a report on the
detection of SARS coronavirus, which instantly went viral in the news.
In the evening, relevant departments also issued an announcement of
"pneumonia of unknown cause", and in the early hours of the 31st,
related rumours also began to spread on Weibo.
6Little Mountain Dog’s posts are in green on the right of the screenshots. In white on the left is whomever she is chatting with on WeChat at the time. Here that
person (most likely another employee of Vision medicals) mentioned on the 26th Dec that someone had pointed out that the WIV is nearby (most likely simply
meaning that it is also in Wuhan city centre - no market is ever mentioned at that stage). Given the timing that ‘someone’ is very likely one of the Vision Medicals
senior people who may also be a mentor or professor. For instance Dr. Xu Teng, Vision Medicals CTO, is also a visiting professor of Yunnan Provincial Key
Laboratory of Gene Editing.
5This is a reference to the Lanzhou brucellosis outbreak that started in July 2019. On precisely the 26th Dec 2019 ajoint investigation had just disclosed that
the outbreak was due to escaped aerosols carried downwind from a vaccine factory, resulting in 200 cases, following detection in November, especially after
students at a nearby downwind institute started falling ill. In the following months, the official tally would climb to 10,528 people infected over 2019, once so many
of the previously undisclosed cases were eventually revealed.
4In the post following one of Little Mountain Dog’s colleagues specifically mentions the WIV which is not far in the city. Hence in the present sentence,
somewhere is likely to be quite specific, by it may also more generally mean any lab in the city doing such work..
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What really made me nervous again was that a friend’s business
shared the sequence for us to analyse. I analysed it and found that it
was indeed the same virus! The first thought in the subconscious is
"this virus is contagious"! It may really be a new type of SARS!
In the middle of the night on the 30th, I got the sequence from a friend’s
business for analysis.
Is there a filtered host, this should be compared to
the human SARS, equivalent to after screening
I only have this one now. How many sequences are
December 30, 2019 at 23:34 pm
Also two by two clusterW?
only 50 or so sequences
December 30, 2019 at 23:42 pm
Two unknown viruses are clustered together, and the similarity is more
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(Because the sequence of the friend business was compared with
SARS, the similarity with SARS reached 93%, while our complete
sequence was about 86%, but the homology between the two was still
close to 100%)
December 30, 2019 23:50 pm
Take ours directly as a reference and
compare their fq directly, the mismatch rate
is very low
OK send data
December 31, 2019 00:02 am
So putting aside the sequence being filtered,
it's basically the same thing
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Pairwise direct comparison, all sequences can be compared, the
similarity is 99.6%, and the similarity between different species is
almost impossible in the conserved region, and the whole genome
coverage rate exceeds 20%, confirming that it is the same virus without
The mood at this time was both nervous and excited. The nervousness
was due to the fact that this unknown virus may be as terrifying as
SARS; the excitement was that we detected and confirmed this
pathogen early through mNGS technology, and quarantined the
patient, so it may be possible to prevent and control the virus before it
spreads widely. Strangled in the cradle!
With mixed feelings and emotions, I immediately posted a circle of
friends that few people can understand.
Countless late nights of working overtime alone, just to
polish better technology, will not be helpless when this
moment comes. The theoretical application in the past has
been confirmed again tonight, and the mNGS technology will
be pushed to the altar…
We are well aware, behind every
precious sample there is a patient
December 31, 2019 00:33 Deleted
On the morning of December 31, rumours about SARS on Weibo
began to spread wildly. I've been waiting to see how the officials would
respond. In the afternoon, the official announcement was issued, only
stating that it was "pneumonia of unknown cause"without
mentioning the pathogen, and that there were 27 similar cases, 7 of
which were severe.
After seeing the news, I felt that things were not good, and I guessed
that the infectious ability of this virus was not low. However, the official
notification is that "no obvious human-to-human transmission has been
found". There is not much data in the early stage, and the situation is
not easy to judge, not to mention [that this is] a new virus. In order to
stabilise social sentiment and avoid excessive panic among the
people, such a notification is actually understandable.
At this time, the expert group has begun to intervene, and the "national
team" such as the Wuhan Institute of Virology has also begun to
analyse and identify. They know more information, have more
samples and data, and are more qualified and professional, so I
will not do much in-depth follow-up. The analysis is done, waiting
for the official results.
At the beginning, I was quite confident in the country's ability to deal
with these sudden and major public health events. After all, it has been
battle-hardened by events such as SARS and influenza A. In addition,
the Beijing plague incident just over two months ago was also detected
and reported by us through mNGS. After the report was communicated
that day, they started the emergency response procedure and
immediately used other methods to verify it again. The next morning I
saw it. The news was out, and no new cases of infection had been
found in the follow-up, and the prevention and control had been done
very well. mNGS has made great contributions to the plague incident,
and I think it can also play a great role in the prevention and control of
this unknown virus.
The media began to refute the rumours. The first time the Beijing News
mentioned "the SARS-related rumours", the People's Daily and others
used a slightly more euphemistic wording, "It cannot be concluded that
it is SARS." The latter eight people who "spread rumours" were
After seeing the news, for some reason, I was suddenly a little
disappointed. Are things that have not yet been conclusive or are
controversial in science, just rumours?
7This is the motto of IDSeqTM, a key technology platform developed by Vision Medicals, which was used in the analysis of the samples on the 26th/27th Dec 19.
See https://archive.ph/VX0Kb. IDSeq trademark was applied for in July 2019.
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There was a feeling that this dispelling rhetoric, as well as that overly
optimistic propaganda, would push the matter into an irreversible
situation. The high-profile refutation of rumours by the media will
interfere with the characterization of this virus science, and the overly
optimistic propaganda would leave the public lacking in respect and not
taking defensive measures. Subsequent developments have once
again confirmed my concerns.
After the incident went viral, some friends also came to ask me if I
knew anything, especially friends from Wuhan. After telling them that
this must be kept strictly confidential (after all, someone was arrested),
I still revealed a little bit of information to them, so that they may pay
attention to protection.
what the heck [blurred, possibly name]
Novel SARS virus
Judging from the number of infected cases,
there may still be a strong transmission
January 2 at 14:44 pm
How much, let me be a little mentally
Let's see if the number of new infections will
be announced in the next two days.
This thing may also be named as some other
coronavirus, but it has a high homology with
the SARS virus. The SARS virus genome
has all the structures it should have. Except
for more mutations, others are basically the
Good to know
The final announcement could be something
like a new bat coronavirus or a new bat
Let's name it something we don't know
Maybe it's not so scary that way.
It's not good to associate it with SARS.
So the name of the previous one is more
This dialogue may also clarify why it is necessary to refute the rumours
about SARS, and the naming of a novel coronavirus. After all, the
genome similarity is only about 80% (off topic, many different strains of
the same type of enterovirus are only 80% similar). SARS has caused
so much trauma to us that the public is extremely panicked by it.
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The similarity of different genes of the new coronavirus compared to
SARS is different, ranging from 75% to 94%. In particular the S gene,
which is related to the human cell receptor (ACE2), is only 75% similar.
Therefore, it is not SARS, and that is a good basis for it.
However, in Shi Zhengli's article later, according to their
methodological analysis, the new coronavirus also belongs to
SARSr-CoV (SARS-related coronavirus).
We all know what happened next. Here are a few more questions.
Q: Why did we conclude that this unknown virus was a
coronavirus very similar to SARS within two days, and reported
all the analysis results, while it took until January 7 for the official
announcement to clarify that the pneumonia was caused by the
In fact, what we did was to analyse and identify such a virus in the
samples submitted for inspection, but whether the pneumonia was
caused by this virus, we did not analyse it, nor could we analyse it. And
the detection of the virus does not mean that the pneumonia was
caused by the virus.
For such a major health event, the officials naturally have to be
rigorous in their arguments, and there is also a set of international
reference verification procedures (Koch's postulates). What the official
has to do is not only to detect that multiple samples have such a virus,
but also to verify that the pneumonia is caused by this virus, etc.
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Koch’s postulates are mainly divided into four steps: 
1. A large number of pathogens can often be found in the diseased
parts of the diseased body, but these pathogens cannot be found in
healthy living bodies.
2. The pathogenic bacteria can be isolated and cultured in the medium
and the characteristics recorded.
3. The pathogenic bacteria cultivated in pure catalpa should be
inoculated into healthy plants of the same variety as the diseased
plants, and produce the same fatigue symptoms as the diseased
4. The pathogen should be able to be re-isolated from the inoculated
diseased strain by the same separation method, and its characteristics
are the same as those of the original diseased strain.
Virus isolation, cultivation, verification, etc. are all time-consuming, and
need to be discussed and agreed upon by experts. It can also be seen
from many papers on the new coronavirus published recently that
many sequencing data were completed in the first two or three days of
There is also a very comprehensible thing about this matter, namely
that those people who know the truth are silent, while those who don't
know the truth are doing all kinds of "strong science" and "in-depth
analysis"; The company I experienced personally did not dare to say a
word, and other companies took advantage of all kinds of marketing.
This is true from the plague to the new coronavirus, hehe, so
To talk about my views on the whole incident, the biggest feelings are
disappointment, sadness, and anger. We have found it so promptly,
why is it still not under control now? Let the whole country enter the
epidemic war? It's not so much up to the science, or the technology,
but to the decision making process and the media.
I used to be a very cynical person. The matter has come to this point
and we can't turn back the clock. Passing on confidence is the most
important thing. After the events everyone is an expert, and no one
would have thought that things would develop like this, so it’s rather
lazy to criticise many things. But there are still some things I want to
Dispelling rumours of SARS and the optimism promoted by the media
were not a big problem in the earliest days, when after all, the
understanding of this virus was very limited. In response to these major
public health events, the CDC may adopt the rules of "internal
strictness and external looseness", with internal caution, strict
verification, and careful evaluation, but external announcements may
be optimistic to avoid causing excessive panic. What's more, in this
incident, how to go public is obviously not something that the CDC can
The status of Wuhan as a transportation hub doesn’t need any
introduction. At that time, the Spring Festival was approaching, which
was the peak season for catering, tourism, movies and other service
industries. Pessimistic propaganda would undoubtedly hit these service
industries hard, and it would also cause excessive panic among the
public, leading to serious consequences such as material looting and
If the virus really has no ability to spread, or because measures are
taken to stifle the spread of the virus, the society does not see what
harm the virus can bring, and policymakers will inevitably be called out
for overreacting and making a big fuss, and then they will naturally take
On the contrary, in the case where the propaganda is too optimistic, if
the virus is not strong, everyone will be happy, and if the virus is strong,
it will cause the public to lack awareness of prevention, and it will be
difficult to carry out prevention and control work, which will eventually
lead to the rapid spread of the virus and more serious consequences.
Therefore, when you are a decision maker, you have to take all factors
into consideration. Social, economic and political aspects need to be
balanced, which will test the ability and foresight of decision makers
Go right, it’s bland. Go wrong, you are a sinner forever.
There are no parallel universes in this world, and we have no way of
knowing which decision is more right or wrong. In the domestic
atmosphere where everyone likes to be optimistic about everything,
and the existence of luck, it is understandable what decision
decision-makers will make.
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (firstname.lastname@example.org), p.18/54
In the later development of the incident, especially starting around
January 12, I believe the experts saw that things were going in a bad
direction (about 30% of the first 41 confirmed patients had no history of
exposure to the seafood market. At this time, suspected cases began
to appear in many places, and some of them were initially positive for
However, in the follow-up, the public messaging is still too optimistic
and artistic, and at the same time, it is still constantly refuting rumours,
and there is no sign of issuing an early warning.
"Limited human-to-human transmission is not ruled out, the risk of
sustained human-to-human transmission is low, and it is preventable
and controllable." The wording is quite cautious, not to mention
whether it is too optimistic, just ask how many ordinary people know
what "limited human-to-human transmission" is? What is "sustained
Their understanding may be that there is basically no human-to-human
transmission, and they are naturally unsuspecting. I also popularised it
in my circle of friends.
Limited human-to-human transmission: A can be passed on to B, C...,
but B, C... will not be passed on to other people.
Continuous human-to-human transmission: A to B, B to C, C to D... can
continue to be passed on
Expert opinion: Wuhan pneumonia does not rule out limited
human-to-human transmission, and scientific prevention requires our
It can also be seen from many papers published now that many
experts had a deep understanding of the spread of this virus very early,
and the more data they had, the clearer the prediction of the situation.
I believe that experts have already given not very optimistic predictions,
but if, in order to take into account the public standing of certain people
or certain media (after all, the propaganda was too optimistic before,
and now it is too painful to face), some people are ignoring the opinions
of experts, disregard the public health, have to make announcements
so optimistic in character and insist on not issuing early warnings - then
that is unforgivable.
No matter who that is, penalise those who should be penalised, fire
those who should be fired.
Without further ado, let's talk about hope.
mNGS is indeed a good technology, which plays a great role in the
diagnosis of difficult and critical cases, as well as in the early
surveillance and outbreak surveillance of such sudden and major
public health events. There are many manufacturers providing mNGS
pathogen detection services. It is suggested that the CDC can
establish direct communication channels with some companies with
good technology, so that it may respond to emergencies like this more
quickly. In addition, mNGS companies can also establish an
information sharing platform to share information in time when
encountering these incidents to see if there is an outbreak (I know this
is difficult. On the one hand, it is a commercial secret. On the other
hand, sensitive pathogens are not reported easily by anyone, but I still
think this matter is very meaningful, and I hope it will become a reality
I also hope that after we have experienced this new coronavirus
incident, the country's ability to handle major public health events has
made great progress. Personally, I believe that the rules of weather
forecasting can be used for reference in announcements and publicity -
"there will always be more harmful aspects to forecast" to remind the
public to take more precautions and reduce psychological
expectations. As the saying goes: without expectations, you will not be
To me, this matter seems to be a year-end exam. I have exhausted
what I have learned and handed in a fairly qualified answer sheet, but
has this answer sheet played the biggest role? For the first time, I
personally participated in such a major public health event, made a
little contribution, and practised and grew a lot.
As far as I know, we should have been the first to discover this virus,
because it was after we reported the results that the CDC began to
intervene. From the data submitted on the GISAID database website,
the time of sample collection is also our earliest. Maybe other
institutions have also detected this virus, but this is an unknown virus,
there is no reference genome in the nucleic acid database, and they
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.19/54
may not have the ability to analyse and identify it.
So, it should be that we were the first to discover this new coronavirus.
Let’s record it.
Hope to overcome the epidemic soon.
Go China! Come on, Wuhan!
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (firstname.lastname@example.org), p.20/54
Post 2: Weixin post by Little Mountain Dog, on the 30th Jan 2020
Statement on "Recording the experience of first discovering the novel coronavirus"
Original (web archive)
Original 小山狗 小山狗 2020-01-30 23:39
Statement on "Recording the experience of first discovering the
Original Little Mountain Dog, Little Mountain Dog 2020-01-30 23:39
1. The text "Recording the experience of first discovering the new
coronavirus" was written for myself to read in the future, but it spread
online and I didn't want to get involved in anything, so I deleted it.
2. Not authorised to any individual or media, all reprints are
unauthorised reprints; and no information has been provided to
3. The heart of imperialism will never die, and any information can be
swayed by external anti-China forces to add fuel to the scandal. More
details in published papers are also more authoritative. If the
information in this article is unfortunately used, it will be a joke.
4. My unit is not any public institution, but only a small private
enterprise located in Huangpu, Guangzhou.
5. I don't want to cause trouble to anyone, and I don't want to stir up
public opinion. The company treated me very well and did not want to
cause any trouble to the company. The company did not know about
my post, and the leaders were understanding and forgiving afterwards.
I grew up with the company and could not live up to the company's
love and expectations for me.
6. I'm still too young, and this matter is too complicated. I just
expressed my own thoughts. I have neither the conditions nor the
ability to judge the development directions of the early epidemic -
these are all hindsights. It's not that I didn't go to the top to make
suggestions, or that I knew the epidemic was so serious but didn't
have the courage to release information to the community at an early
stage, but I really didn't have the ability to know anything about the
development of the whole epidemic.
7. I just want to devote myself to researching technology and do
research well. Whether it can benefit the people on one side depends
on luck. I do not want to be disturbed by any attention, so everyone,
please just leave.
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.21/54
Post 3: Weixin (poetic) post by Little Mountain Dog, on the 4th Apr 2020
“When the ‘prophecies’ of the epidemic came true one by one, I dared not speak"
Copy (web archive)
Original 小山狗, 小山狗 2020-04-04 06:49
Statement on "Recording the experience of first discovering the
Original Little Mountain Dog. Little Mountain Dog 2020-01-30 23:39
April 3, 2020
Confirmed cases of new coronavirus infection worldwide exceed 1
To put it mildly it’s dramatic
As early as January 23
When Wuhan first closed the city
I said this in a friends chat group:
January 23 at 17:18 pm
It is conservatively estimated that the number of
infections this time will exceed one million,
including those undetected
Now the number of people diagnosed is more than that
When including those who have not been detected it is much more than
I don’t think it really is one.
Most of this was said casually, intentionally or unintentionally.
Or just a gut feeling
There were only a few hundred cases diagnosed at the time.8
I said it was to infect more than a million people
Almost no one believed it
But the reality is unexpected
It's not scary that such a prophecy came true.
The scary thing is that almost all my casual predictions have come true
The plot really went according to my intuition.
I'm scared myself
At the very beginning there is nothing more than this
Back then was just diagnosed as a new type of coronavirus:
December 27 at 09:51 am
It's not good, another serious public health
Then the epidemic really broke out
I really didn't know anything back then.
We only knew about this one such patient,
We thought it was an isolated case,
A previously discovered
Bat SARS-like virus,
Basically they don’t infect people.
This may be an accidental infection.
It won't spread, right?
However, I always had a bad feeling.
I was worried for two days
- It felt so weird -
Before I asked a question:9
9She asked the question that follows on the 29th Dec, two days after the previous post dated 27th Dec.
8On the 23rd Jan 2020 (when Little Mountain Dog made her prediction) there were 639 cases worldwide according to this site. On the 4th April 2020 (when she
wrote that blog entry), there were 1.19 mln cases.
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December 29, 2019 17:14 pm
I don't know if there will soon be any news of an
December 29, 2019 17:17 pm
December 31, 2019 00:04 am
Feeling that something is wrong
Sure enough, there was some news on the evening of December 30,
Announcement of Unknown Pneumonia by the Wuhan Health
SARS spread on Weibo
That's not an isolated case!
Before the epidemic broke out on a large scale,
Persuaded others to take precautions.
I said that the severity is not lower than SARS,
That Huanan seafood market is not necessarily the source:10, 11
January 17 at 22:46 pm
It's not as serious as SARS anyway
Wrong, it's just the beginning, but now the
detection technology is good, with a fast
The Wuhan seafood market may have been
infected by a super-spreader, it’s not
necessarily the source
The new crown epidemic is of course more serious than SARS.
Molecular Evolutionary Analysis,
Has basically been ruled out that the South China Seafood Market is
Possibly a superspreader.
The closest way
May be to speculate based on some trends
That's right, it's normal:
March 19 at 13:22 pm13
The United States is about to break 10,000
cases, and it is estimated that it will overtake
China in just a week
13 The US had 9,169 cases on March 18th, then 13,663 one day later. The US overtook China on March 25th. See this site.
12 Here she is introducing the next post dated March 19th. The ‘Epidemiological Investigation’ and ‘Molecular Evolutionary analysis’ refers to points published after
the date of her previous post (17th Jan) where she made that statement about the market not necessarily being the source. The articles mentioned above are
good examples of such research that was published between Jan 17th and Mar 19th.
11 The timing (17th Jan post) of that statement is surprising, as it was made very early. Only on the 17th Feb 2020 would a team of scientists from Guangzhou
(where Vision Medicals is located) sent an article for publication that concluded that the virus appeared around November 2019, hence before the market
outbreak, based on genome evolution. Then on the 19th Feb 2020 a very unlikely team led by conservation biologists from Yunnan published a remarkable paper,
on a Chinese preprint site, that systematically rejects the wet-market hypothesis based on a careful analysis of available sequences to that date. The 19th Feb is
also two days be the first WHO team arrived in China (17-22 Feb 2020)
10 The main implication being that human to human transmission is then a likely reality. As long as cases can be confined to the market, one can still hope (or
pretend) that there is no human infection - at least for a while. This is exactly what the Chinese authorities were saying until the 20th Jan 2020, 20 days after the
market was closed and so at a time when insisting on market related infections (from some host animal) just couldn’t make any sense any more. See this
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Sure enough, it would overtake China in about a week.
If all the possibilities are predicted,
There's bound to be a collision.
It’s not surprising.
But my prediction about the epidemic,
Or my views on the epidemic,
That’s all I’ve said,
They’ve all come true
This is what scares me
Why does the plot keep going in the direction I want it to go?
It's not all very dark, right?:
There must be more
The peak period is expected to be in
March~April, at that time it is no different from
Do a test for yourself tomorrow, go home if
there is no problem
Going back, my relatives and friends came back
from Wuhan yesterday
Two weeks in isolation
January 21 at 19:35 pm
The outbreak in Guangdong was in February14
After the temperature rises, it gradually recedes
towards the north
You have already figured this out very clearly
Just my intuition
It was said earlier that the peak period is in March-April.
I hope so
One more month and it will be over
The dawn of the world is coming
I still feel weird
How come most of them came true?
It feels like the “Truman Show”15
Everything is arranged by the director
Are you all actors?
Am I Truman?
No matter which city you are in
There is always a sense of déjà vu with the people around you
They looks the same
Similar body type
Dressing the same
Could it be that the same group of actors
Wearing different costumes?
Of course there are unreal words
Confirmed cases worldwide:
15 Little Mountain Dog is a film lover.
14 She is referring to the SARS outbreak in Guangdong in Q1 2003. See this link.
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March 10 at 16:36 pm
The United States will contribute at least half
It's not schadenfreude
It is based on the epidemic prevention measures of the US
The size of the population of the US
Their big city population density
Socialising is still more frequent
Too stubborn to wear a mask
No mathematical model
Just consider it nonsense
Little by little it came true
Maybe I am such a jinx
I won't talk about it anymore
Dare not say it
January 14 at 11:48 am
This is a tough battle, the Spring Festival is not
making it easy
I'll just see how many officials have resigned
January 14 at 11:49 am
This is not the way to maintain stability. The
warning that should be issued should still be
The mortality rate is not high, but it is not nice to
have severe pneumonia
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.25/54
Doc 4: Weixin post by Little Mountain Dog, on the 24th Feb 2020
Question | Are pangolins the intermediate host of the new coronavirus? Rodents may also be possible
Original (web archive)
质疑 | 穿山甲是新冠病毒的中间宿主么？啮齿类或许也有可能
Original 小山狗 小山狗 2020-02-24 00:11
吧，拉丁学名为Human coronavirus 2019，缩写HCoV-2019，中文简称
Question | Are pangolins the intermediate host of the new
coronavirus? Rodents may also be
Original Little Mountain Dog, Little Mountain Dog 2020-02-24 00:11
I didn't want to write anything anymore, but there are always some
ideas in my mind, and I always think about other ideas that interfere
with work and life. Time and energy are always limited, I should be
very tired and unfocused thinking about this and that. So I still write it
down. It’s always been like this before. I don’t have to worry about it
anymore when I write it down. It can be quickly forgotten.
In addition, I looked at the background data of these several posts.
The open rate on my post is about 2~3%. If there is no forwarding,
then it is estimated that the volume of readers will be around one or
two hundred, which is quite safe, so it will be more casual to write
anything going forward.
Everything I write is to record my thoughts or experiences, not to do
popular science. The above is all nonsense, let the text begin.
After the International Committee on Taxonomy of Viruses proposed to
name the new coronavirus SARS-CoV-2, this name was adopted in
both media articles and scientific papers, but this is not the final name,
it is controversial and may change, although the possibility is very
small. In response to the call of domestic experts, before the final
official name, I will write something later, I will call the new coronavirus
according to the human coronavirus 2019, the Latin name is Human
coronavirus 2019, abbreviation HCoV-2019, Chinese abbreviation
human coronavirus 19.
Since the South China Agricultural University (SCAU) announced that
pangolins are potential hosts of human coronavirus 19, pangolins have
become a hot topic. In the past few days, several research preprints on
pangolin coronaviruses have also been produced.
To be honest, after seeing the SCAU press conference16 at that time,
although I kept my doubts, I was still looking forward to it. After all, it
was said at the press conference that the virus had been isolated, and
the genome analysis showed that the sequence similarity was 99%. At
that time, I thought that if the similarity of the whole genome is 99%,
then the possibility of pangolins being the intermediate host is very
high, which is of great significance to the traceability of the virus.
16 The South China Agricultural University (SCAU) press conference was held on the 7th Feb 2020. See here for the official Weixin post from SCAU, and see
video extract. That conference was controversial for its announcement of a pangolin virus with 99% similarity to SARS-CoV-2. This was a misrepresentation; the
similarity is much lower on the whole genome, the 99% only refers to the RBD (Receptor-Binding Domain).
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However, after the paper17 and data were made public, I was very
disappointed, and I could only sigh at the breadth and depth of the
language. It's "sequence similarity". I didn't say it was whole genome
similarity, right? After all, some gene fragments can reach 99%! (I
really don’t dare to say that I lost my face and left the country,
otherwise my article will be deleted shortly. How many domestic
and foreign colleagues or non-peers are watching? Should we use
more rigorous words in the press conference?)
What did SCAU paper say? It was probably just an aggressive
operation, and directly analysed a large number of metagenomic
sequencing data from the public database, and found that there are
some sequences very similar to human coronavirus 19 in the pangolin
sequencing data (the idea is worth learning from, make good use of
public resources), so I quickly took samples of pangolins for analysis,
and found that about 70% (17/25) of Malay pangolins carried
coronavirus (not necessarily all of the same), and successfully isolated
a virus similar to human coronavirus 19. (The whole genome similarity
is only 90.3%, not 99% as the news said at the time), named
Pangolin-CoV. The amino acid homology of E, M, N and S genes was
100%, 98.2%, 96.7% and 90.4%, respectively; the receptor binding
domain (RBD) of S protein differed by only one amino acid. This RBD
is the key to combining with AEC2, and it is also an important basis for
the conclusion of the SCAU article.
(Screenshot of SCAU paper, similarity of different genes between
Pangolin-CoV and various coronaviruses)
Serological analysis shows that pangolins have antibodies that can
react with human coronavirus 19, indicating that they may have been
infected by related viruses! Pathological analysis showed that
17 SCAU sent its preprint to BioRXiv on the 17th Feb where it was published on the 20th Feb 2020. All the extracts in Little Mountain Dog’s posty (dated 24th Feb)
are from that preprint. The manuscript was also sent to Nature on the 16th Feb, accepted on the 28th April and published on the 7th May 2020.
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pangolins did show signs of infection, indicating that the virus could
The overall similarity between Pangolin-CoV and HCoV-2019 is still not
as high as 96% of RaTG13, and only the RBD region is the highest in
Pangolin-CoV. Through genome evolution and recombination analysis,
the authors believe that human coronavirus 19 may originate from
Pangolin-CoV-like Recombination of virus and RaTG13-like virus.
(SCAU paper, Pangolin-CoV and various coronavirus genomes are
similar, among which Pangolin-CoV and HCoV-2019 in the RBD region
have the highest similarity)
Some other analyses will not be introduced. Anyway, the author's
conclusion in the end is that pangolins are reasonable intermediate
hosts, and everyone must protect the wild animals such as pangolins.
Objectively speaking, there is nothing wrong with the paper itself, and
it is very good. As for whether the conclusions in the paper can be
drawn, it feels a bit far-fetched and not very persuasive, but this thing
is that the benevolent sees the benevolent and the wise sees the
wisdom. Losing in the early press conference gives people too much
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Guan Yi’s team also published a similar preprint18, and also found 2
types (8 strains clustered into 2 close categories, each type should be
the same type) viruses that are very similar to human coronavirus 19,
supporting the idea that pangolins do indeed carry this type of
coronavirus, and also suggesting that pangolins may be intermediate
hosts for human coronavirus 19. However, the authors believe that
human coronavirus 19 and pangolin coronavirus are more likely to be
caused by convergent evolution rather than recombination.
此外陈金平团队则直接发布了题目为《Are pangolins the intermediate
host of the 2019 novel coronavirus (2019-nCoV) ?》的预印文章，也是
(Photo of Guan Yi's team's paper, pangolin coronavirus and human
coronavirus 19 gather on a large branch)
In addition, Jinping Chen's team directly published a preprint19 entitled
"Are pangolins the intermediate host of the 2019 novel coronavirus
(2019-nCoV)?", which also found that pangolins carry viruses similar to
human coronavirus 19. However, the authors believe that their
research suggests that pangolins are the natural host of Beta
coronavirus and may infect humans, but do not support pangolins as
an intermediate host for human coronavirus 19.
19 Preprint released on the 20th Feb 2020. See https://www.biorxiv.org/content/10.1101/2020.02.18.954628v1.article-info.
18 Preprint released on the 18th Feb 2020, see https://www.biorxiv.org/content/10.1101/2020.02.13.945485v1.article-info. The Nature version has a ‘received’ date
of the 7th Feb 2020. Eddie Holmes joined that team after the Farrar/Fauci conference call on the 1st Feb 2020 to help with the writing.
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(Chen Jinping's team's paper map, pangolin coronavirus is also very
close to human coronavirus 19)
In fact, the analysis methods and data of these studies are similar, but
the conclusions drawn are not the same.
The pangolin coronavirus genome data of these three studies have
been made public, so I can use these data for analysis, and simply
compare the similarity to see the differences between these
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (firstname.lastname@example.org), p.30/54
The average similarity map of the whole genome of pangolin
coronavirus and other viruses, the red font is from the paper of Guan
Yi's team, the purple SCAU team, the blue Chen Jinping team, the
green is human coronavirus 19, SARS and bat-SARS-like black)
As can be seen from the above picture, the pangolin coronaviruses of
Guan Yi's team, SCAU team, and Chen Jinping's team may be
different species, but the pangolin coronavirus of SCAU team and
Chen's team may be the same! Because the similarity between the two
strains reaches 99%, the pangolin coronavirus in Chen Jinping’s team
has not been sequenced completely, and the quality may not be high.
Therefore, excluding quality problems, the similarity between the two
strains may be greater than 99%, which is extremely likely to be the
same coronavirus. Big! Interestingly, their article came to the opposite
Based on the above studies, according to the only data on pangolin
coronaviruses available at present, my opinion is that it is extremely
unlikely that pangolins are the intermediate host of human coronavirus
19, or not at all. There is only about 90% similarity, the difference is too
big, at least it has to go through another intermediate host. Even
though the similarity of the RBD region of the S protein is relatively
hgh, the other regions have an overall 10% difference, that's many
years it would take to complete the mutation. RaTG13 overall
difference is only 4%, and the evolution time required is shorter. It
might as well be a direct infection from the bat. After all, RaTG13 was
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.31/54
collected 7 years ago, and mutated in wild bats for 7 years, it is entirely
possible to mutate into today's human coronavirus 19.
So is pangolin safe? Not at all, the pangolin coronavirus is also very
likely to infect humans, and it is still a problem in the RBD area, which
is too similar to the human coronavirus 19. Not only is it possible to
infect people, but it may also be as terrifying as the human coronavirus
19, SARS virus and MERS virus, because at present, the new
BetaCoV that can infect people is these three, and each of them is a
strong general. I feel that I can raise the alarm when I encounter
BetaCoV that can infect people in the future. It can be seen from
Huanong's article that the proportion of BetaCoV-positive pangolins is
still very high, so stay in awe!
At this point, it seems that there is no hope in finding the intermediate
host of human coronavirus 19. If the intermediate host is not found, if
the intermediate host is by our side, then it will be a ticking time bomb
that can cause the epidemic to recur.
I had previously guessed that rodents were very suspicious. A reader
reminded that a paper had done a binding experiment between the
human coronavirus 19 S protein and the mouse AEC2 protein, and it
seemed that it would not work.
After reading it, I found out that it was Shi Zhengli's article20. At that
time, I didn't notice the animal experiments in it.
20 The link that she was pointed to in that exchange is https://www.biorxiv.org/content/10.1101/2020.01.22.914952v2.full.pdf.
https://www.biorxiv.org/content/10.1101/2020.01.22.914952v2 is a preprint by Shi Sheng-Li published on the 23rd Jan 2020. The paper was eventually published
in Nature on the 3rd Feb 2020 (https://www.nature.com/articles/s41586-020-2012-7).
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Although different kinds of rodents may be a little different (rats, mice,
voles, etc.), there should be no big difference. If the experimental
model is OK, then the suspicion of rodent is less. Otherwise, the
Academy of Medical Sciences may not have to work so hard to
construct a mouse model of human AEC2 gene (but even if it can be
combined, it may be quite different from that of humans, and a
transgenic model may be necessary).
On January 22, the Ministry of Science and Technology launched
the first batch of emergency projects for new coronavirus scientific
and technological research, and determined that the Institute of
Medical Laboratory Animals of the Academy of Medical Sciences
presided over the construction of animal models. Subsequently, the
institute worked closely with the Chinese Center for Viral Disease
Control and Prevention and other units, and successfully established
a transgenic mouse model and a rhesus monkey model on January
29 and February 14, respectively. At present, the above models
have been applied to the research of pathogenic mechanism and
transmission route, emergency drug screening and vaccine
evaluation. (Chief reporter Liu Zhiyong)
From the current investigation and research, the potential possibility of
intermediate hosts should be basically ruled out.
The scientific research team of the China Center for Animal Health
and Epidemiology has tested more than 4,800 samples of poultry
and livestock (including chickens, ducks, scallops, pigs, dogs, cats,
etc.) The nucleic acid test of the new coronavirus in the samples
was negative, which ruled out the transmission route of the new
coronavirus that caused the outbreak from poultry and livestock..
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.33/54
The above methods are all found through the virus itself, and
comparing the similarity of the virus is of course the most direct. So
can we look at it from a different angle? Looking for a virus directly is
like looking for a needle in a haystack, and there is no hope in sight, so
is it possible to screen from the most likely host? How to find the most
likely host? Maybe the protein ACE2 can help. We can try to analyse
from the host to see which animals have the most similar ACE2
proteins to humans, and even find the regions bound by RBD with the
highest similarity, and then screen after certain animals.
Just do it, start with the public database, and directly compare the
human ACE2 with the NCBI protein database (nr).
Sure enough, except for one synthetic, the rest are non-human
primates. From this perspective, non-human primates are the biggest
suspects, but even the intermediate host is not the biggest hidden
danger. Still have to pay attention to other animals.
Take the top 100 and look at the evolutionary tree.
It can be seen from the evolutionary tree of the full-length ACE2 that
the evolutionary relationship between pangolins and humans is
relatively far away. Except for primates, the closest evolutionary
relationship is rodents. Rabbits also seem a more likely suspect.
After excluding primates, we compared them again, and the most
similar ones turned out to be squirrels? Might have to catch a few
squirrels to test it out.
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (firstname.lastname@example.org), p.34/54
But the key to ACE2 should be the region that binds to the RBD region
of the S protein of human coronavirus 19, that is, the ACE2-PD region.
Just repeat the above analysis with ACE2-PD.
Excluding primates, the most similar is the civet cat, and it has a
similarity of 98%! The similarity is higher than that of many primates.
No wonder the intermediate host of SARS is the civet cat! Wouldn't the
intermediate host of the human coronavirus 19 this time also be a civet
cat? In this case, would it be also helpful to find the intermediate host
through the homology analysis of ACE2-PD? It's a pity that other than
civet cats, there are no other species with such a high degree of
In addition to primates and civet cats, the homology analysis of
ACE2-PD is most similar to some rodents that do not know what they
are called (not mice, but degus, naked mole rats, hamsters, etc.), but
only Less than 90% similarity.
The evolutionary tree looks like this:
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.35/54
Pangolins are still not as homologous as rodents, and they are more
likely to feel rodents than pangolins.
To sum up, analysing the host from the perspective of ACE2 homology,
non-human primates have the highest homology, but if non-human
primates are intermediate hosts, then these viruses are very likely to
directly infect humans without the need for through the intermediate
host of non-human primates. The civet cat is still suspected, but it is
estimated that it has been tested a lot, so the most likely thing left is
the rodent, and the homology is higher than that of the pangolin.
Degus, naked mole rat, hamster, etc., as well as rabbits, hares, etc.
are all worth studying.
Of course, this method is also flawed. After all, it is only analysed from
the public database. If the real intermediate host has not been
sequenced at all, then there is no sequence of the ACE2 protein, so it
cannot be analysed. What's more, this is only on paper, and the
problem can only be explained by the detection of highly homologous
viruses by experimental means.
In addition, Wuhan may not be the birthplace of patient 0? Maybe the
outbreak occurred after being infected from other places and brought
to Wuhan? Therefore, the search for an intermediate host cannot be
limited to Wuhan. Maybe we can take another bat sample to see what
the RaTG13-related virus has evolved into now. Is it similar to the
human coronavirus 19? Maybe it was passed directly from the bat?
Finally, the research on pangolin coronaviruses by the SCAU team is
still of great value and inspiration. At least it allows us to know that
pangolins carry many viruses similar to human coronavirus 19, and the
RBD region of the S protein is also highly similar. It is likely to infect
people, and it is of great value from a preventive point of view. But I
don't think any of these studies support pangolins as an intermediate
host for 2019-nCoV. Rodents Worth Studying Based on Homology
Analysis of ACE2
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Annexe 1 - Caixin articles
On the article:
There are 3 versions of the article.
1. The Full Caixin article (in Chinese) which is most detailed and was quickly deleted (https://archive.li/YylMt#selection-499.3-499.22)
2. A Caixin blog entry (in Chinese) (https://zhuanlan.zhihu.com/p/109427040) which is still available and is the same as (1) without the last
2 of the 4 sections (so half size). It included at the end a link to the full version (1) above.
3. A short Caixin article in English which is much more limited and still available online via asia.nikkei.com.
This article (in form 1) is explicitly mentioned by Little Mountain Dog on Weixin:
First of all, I have to admire the reporters from Caixin.com, who dug up so much accurate information from the messy information in the
early days, and wrote an article titled "New Coronavirus Gene Sequencing Traceability: when did the alarm sound."
Since writing about that experience, many reporters wanted to interview, including Caixin.com. They made more than one phone call (too
many reporters, I can't remember how many repeats), but refused. Later, they basically restored the whole incident from clues. Later,
many other organisations also sorted out the timeline based on this report.
The Caixin article seems to have been accompanied by a detailed Timeline chart, now deleted but preserved in her blog entry (very much worth
#1. Full article (Chinese) of the 26th Feb 2020 @22:10:
This Caixin article seems to have been deleted within one day
-Here is the 404’d original link: http://china.caixin.com/2020-02-26/101520972.html
-Web Archive of the original link: https://archive.li/YylMt#selection-499.3-499.22
- A full translation with side by side Chinese and English.
Exclusive | New coronavirus gene sequencing traceability: when the alarm was sounded
February 26, 2020 22:10 Source: Caixin.com
The isolation, detection and gene sequencing of the new coronavirus are the basis for understanding and determining the infectiousness and
harmfulness of the new coronavirus epidemic. On January 11, the Wuhan Health Commission, which had stopped giving updates for several days,
changed the name of "viral pneumonia of unknown origin" to "pneumonia of novel coronavirus infection" for the first time, saying that as of January
10, 2020 24:00, there were 41 cases of preliminary diagnosis of new coronavirus pneumonia.
On December 30, the Institute of Virology of the Chinese Academy of Sciences got the virus samples, January 1, 2020, virus isolation, January 2, completed the
gene sequencing of the virus, January 5, isolated the virus strain, January 9, completed the national virus repository into the library and standardised storage.
[Caixin.com] (Reporter Gao Yu, Peng Yanfeng, Yang Rui, Feng Yuding, Ma Danmeng)
Tracing back the roots of the new coronavirus, which has killed more than 2,660 people and caused more than 77,000 confirmed infections as of
Feb. 24, when was this new coronavirus, similar to SARS, discovered? The Caixin reporters went through multiple interviews, and combed
through the relevant papers, database information corroboration, so that the information puzzle gradually fully emerges.
All kinds of evidence show that before the end of December last year, samples of no less than nine unidentified pneumonia cases were collected
from various hospitals in Wuhan, and genetic sequencing showed that the pathogen was a type of SARS coronavirus, and these test results were
successively returned to the hospitals and reported to the Health and Welfare Commission and the CDC. On January 9, CCTV reported that the
"Wuhan Viral Pneumonia Pathogenic Test Results Preliminary Evaluation Expert Group" officially declared the pathogen as a "novel coronavirus".
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.37/54
The first case was released on December 27
On December 15, 2019, a 65-year-old male delivery man from the South China Seafood Market began to develop a fever. On December 18, he
came to the emergency department of Wuhan Central Hospital Main Hospital (Nanjing Road Campus) to see a doctor, who suspected that it might
be community-acquired pneumonia and admitted him to the emergency department ward of the hospital. Community-acquired pneumonia is a
general term for pneumonia caused by a variety of microorganisms, including bacteria, viruses, chlamydia and mycoplasma, with the main clinical
symptoms being cough, with or without sputum and chest pain.
On December 22, this patient's condition worsened and he was admitted to the ICU, where doctors used various antibiotics to treat him without
results. Professor Zhao Su, chief physician of the Department of Respiratory Medicine at Wuhan Central Hospital, told Caixin that on December
24, a deputy chief physician of the Department of Respiratory Medicine performed a tracheoscopic sampling of this patient, and then sent the
patient's alveolar lavage fluid sample to a third-party testing organisation, Guangzhou Weiyuan Gene Technology Co. for NGS testing, hoping to
use its second-generation high-throughput gene sequencing technology (mNGS) based on macrogenomics, to identify the pathogen. Alveolar
lavage is a therapeutic method to remove inflammatory secretions, etc. from the alveoli and improve respiratory function. For lower respiratory
tract and lung diseases, the pathogen content in alveolar lavage fluid is higher than that in pharyngeal swabs.
Vision Medicals, whose full [Chinese] name is Guangzhou Weiyuan Gene Technology Co., was established in June 2018. Its communication says
it focuses on precision medicine in oncology and infection pathogenesis and has a sequencing platform (NGS) based on second-generation
high-throughput sequencing technology.
"Since BGI started using sequencing technology, there have been many gene sequencing companies in China, large and small. Over the years, in
our various medical seminars, the second-generation high-throughput gene sequencing technology has been continuously introduced, and these
companies have also sent pharmaceutical companies. Representatives go to major hospitals to preach." Zhao Su told Caixin reporters.
The full name of BGI (300676.SZ) is Shenzhen BGI Co., Ltd., formerly known as Beijing BGI Research Center, Founded in 1999, it has
successively completed a number of genome research projects at the international advanced level, including the Chinese part of the International
Human Genome Project, the Rice and Giant Panda Genome Projects, etc. In July 2017, it was listed on the Growth Enterprise Market with the
"First Gene Sequencing Unit", and it is the world's largest genomics R&D institution. Another doctor at the Wuhan Union Hospital also introduced,
"Test once, 6 million base sequences, 3,000 yuan, the 3,000 yuan can find out what the pathogen is a virus or bacteria, it may save lives."
Generally speaking, the gene sequencing company should give feedback on the test results three days later, on Dec. 27, but Weiyuan Gene did
not give a written report. "They just notified us by phone that it was a new coronavirus." Zhao Su said. By this time the patient had been
transferred to Wuhan Tongji Hospital on Dec. 25.
On Feb. 21, 2020, the genetic test information of this case was disclosed in an article by the WeChat public website "Weiyuan Gene”. According to
the article, the Chinese Medical Journal (English version) published a paper on January 27 about the discovery of the new coronavirus and the
involvement of Weiyuan Gene in the early detection of the new coronavirus.
The aforementioned paper published in the Chinese Medical Journal refers to the article "Identification of a novel coronavirus that causes severe
pneumonia in humans: a descriptive study" published on January 29. The authors of the paper are from the Institute of Pathogen Biology, Chinese
Academy of Medical Sciences/Beijing Union Medical College (hereafter referred to as the Institute of Pathogen Biology, Chinese Academy of
Medical Sciences), China-Japan Friendship Hospital, Hubei Provincial CDC, Wuhan Jinyintan Hospital, Wuhan Central Hospital, and Guangzhou
Weiyuan Gene Technology Co. Xu Teng, chief technology officer of Weiyuan Gene, is the co-first author of the paper, and Li Yongjun, CEO, and
Wang Xiaorui, chief operating officer, are the byline authors. Li Yongjun was a bioinformatics analyst at the Institute of Pathogen Biology, Chinese
Academy of Medical Sciences.
According to the paper, the researchers collected clinical data and bronchoalveolar lavage samples from five patients with severe pneumonia at
Jinyintan Hospital in Wuhan, Hubei, and performed pathogenic macrogenomics (mNGS) analysis. As a result, a coronavirus with 79% nucleotide
sequence similarity to SARS virus, which has never been reported before, was found in all these samples. The paper shows that the first clinical
sample from these five patients to be genetically sequenced was a sample from a 65-year-old patient collected on December 24. He developed a
high fever and cough with little sputum on December 15. He was admitted to the hospital on the 18th and to the ICU on December 22. 16 days
later he still had a persistent high fever that developed into severe shortness of breath.
Also highly consistent with the above information is an article titled "Record the experience of discovering the new coronavirus for the first time"
published by the WeChat public account “Little Mountain Dog” (Xiaoshan Gou) on January 28. The author claimed to be working in a private
enterprise in Huangpu, Guangzhou, and recorded in the article: "I just went to work on December 26, 2019, and as usual, I first browsed through
the mNGS pathogenic microorganism automatic interpretation results for the day. Unexpectedly, I found that one sample reported a sensitive
pathogen - SARS coronavirus, with dozens of sequences, and only this sample had such a meaningful pathogen. With a tight heart, I hurriedly
checked the detailed analysis data in the background and found that the similarity was not very high, only about 94.5%. In order to confirm the
reliability of the results, a detailed analysis was started. The results of the exploratory version of the analysis suggested that this pathogen was
most similar to Bat SARS like coronavirus (bat-like SARS coronavirus), with an overall similarity of about 87%, while the similarity to SARS was
According to the author, the patient's sample was also collected on December 24. The article mentions that "the front-end feedback is that this
patient is seriously ill, the test results are urgently needed but such a significant pathogen really cannot be reported easily, so I had an urgent
meeting with several company bosses at noon and decided to continue the in-depth analysis and delay the release of the report, while sharing the
data with the Institute Pathogen Biology of the Chinese Academy of Medical Sciences so that they can get a piece of the analysis". The Institute
of Pathogen Biology of the Chinese Academy of Medical Sciences is one of the authors institutions for the above-mentioned paper in the Chinese
Medical Journal (English version), and the CEO of Weiyuan Gene, Li Yongjun, worked for the Institute of Pathogen Biology of the Chinese
Academy of Medical Sciences, whose immediate superior, the president of the Chinese Academy of Medical Sciences, is academician Wang
Chen, vice president of the Chinese Academy of Engineering.
On Dec. 27, the lab assembled a near-complete sequence of the viral genome, and the data was also shared with the Institute of Pathogen
Biology of the Chinese Academy of Medical Sciences. "It was basically confirmed that this patient's sample did have a novel virus similar to Bat
SARS like coronavirus inside." The article writes, "The information received at the time was that this patient had been back to his hometown and
exposure to bats could not be ruled out. Aware of the potential seriousness of the problem, the laboratory was fully cleaned and disinfected,
samples were harmlessly destroyed, and the personnel involved in the experimental operation were monitored for this. We have communicated
with the doctor before noon, the patient was also isolated."
"It should be that we first discovered this new coronavirus." The article by "Little Mountain Dog" also gives a screenshot of the GISAID database,
"From the data submitted on the GISAID database website, the earliest sample collection time is also for us."
GISAID is a global platform for sharing data on influenza viruses, and researchers can upload their extracted viral genetic sequences after
registering. Each strain is given a unique number, and information such as the time of collection, date of submission, and laboratory of submission
is also recorded. The Caixin reporter checked and found that, according to the sample collection time, the earliest gene sequence of a new
coronavirus on GISAIDS was collected on December 24, 2019 and uploaded by the Institute of Pathogen Biology of the Chinese Academy of
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Medical Sciences on January 11. This is the sample sequence marked in the screenshot of the article "Little Mountain Dog" that their company
participated in testing.
The article also mentioned that the company's leaders communicated with the hospital and the CDC (department) by phone on December 27 and
28, and even personally went to Wuhan on the 29th and 30th to report and exchange all the analysis results with the hospital and CDC leaders in
person, "including all our analysis results and the analysis results of the Institute of Pathogen Biology of the Academy of Medical Sciences.
Everything is under intense, confidential and strict investigation (at this time, people at the hospital and CDC already knew that there were several
similar patients, and had already started emergency treatment after we communicated the test results)".
The owner of the earliest known sample to complete the genetic sequencing mentioned above, later died in Jinyintan Hospital. The results of this
research, which had detected the new outbreak virus on December 27, also did not play any role at that time.
"SARS coronavirus" exploded on social media
In fact, in addition to the earliest known case, at the end of December 2019, there were two other cases of "unexplained pneumonia" in Wuhan
Central Hospital where samples from patients were sent to different institutions for genetic sequencing. The test results of these two cases had a
significant impact on the disclosure of the outbreak by different pathways.
On December 27, a 41-year-old man surnamed Chen visited Wuhan Central Hospital Nanjing Road Campus. "He is an accountant, his family lives
in Wuchang, has not been to the South China Seafood Market in Hankow at all, probably on December 16 without obvious cause began to fever,
the highest temperature of 39.5 ° C, accompanied by palpitations, chest tightness, breathing difficulties after activity, physical strength decreased
significantly, first on December 22 in the Jiangxia District First People's Hospital to see a doctor, no improvement. " Zhao Su revealed to the Caixin
reporter, "he is an acquaintance of a doctor in our hospital, was transferred to our hospital on the 27th, also admitted to the emergency
department." In the evening of December 27, the patient had a bronchoscopy sample done in the hospital's respiratory ICU, and this time the
sample was sent to another company engaged in NGS testing, Beijing Boao Medical Laboratory Co.
On December 30, the Beijing Boao Medical Laboratory sent the patient's test report back to the doctor, and the test result was directly "SARS
coronavirus" (SARS coronavirus).
The test report of the Beijing Boao Medical Laboratory obtained by the Caixin reporter showed that high confidence positive indicators for SARS
coronavirus and Pseudomonas aeruginosa were detected in the patient's sample. The SARS coronavirus is explained therein as a single-stranded
positive-stranded RNA virus that is transmitted by proximal droplet transmission or contact with the patient's respiratory secretions and can cause
a specific type of pneumonia, also known as atypical pneumonia, that is significantly infectious and can involve multiple organ systems.
"Their gene pool is not complete enough, or maybe they didn't do a review, so they made a small mistake, which is the fact that the virus is
actually not the same thing as SARS, but a new coronavirus", a gene sequencing expert revealed to Caixin reporters.
However, it was the test report that contained a small mistake that directly caught the attention of Wuhan doctors who blew the alarm whistle to the
public through social media, saving the lives of a considerable number of people to some extent.
On December 30, the test report of Beijing Boao Medical Laboratory appeared on the WeChat of a doctor at Wuhan Central Hospital. At 17:48 that
evening, Li Wenliang, an ophthalmologist at Wuhan Central Hospital, posted a message among his classmates: "7 cases of SARS were
diagnosed in the South China Fruit and Seafood Market, and they are quarantined in the emergency department of our hospital"; at 19:39, the
Wuhan Red Cross Society Liu Wen, a neurologist at the hospital, posted a message in the work WeChat group "Concordia Red Cross Society",
saying: "A case of coronavirus pneumonia has just been confirmed in the Houhu District of the Second Hospital (i.e. Wuhan Central Hospital).
Maybe the surrounding areas in South China will be quarantined." "SARS has basically been determined, nurses and sisters, don't go out to shake
it"; at 20:48, Xie Linka, a doctor at the Cancer Centre of Wuhan Union Medical College Hospital, posted a message in the WeChat group of the
cancer centre, "Don't go to the Huanan Seafood Market in the near future, it is happening there now. Many people have suffered from pneumonia
of unknown cause (similar to SARS). Today, our hospital has treated many patients with pneumonia in the Huanan Seafood Market. Everyone
pays attention to wearing masks and ventilating.” These three doctors have since been admonished by the police.
On the same day, the author of the article, "Little Mountain Dog" in Huangpu, Guangzhou, was also informed of the above news, she recounted:
"By December 30, I heard the news that there were more than a few patients with similar symptoms, and my nerves were suddenly tense. In
particular, about the afternoon of the 30th, a friend’s company may have detected the same virus in another patient's sample, but they directly sent
a report of the detection of SARS coronavirus, which instantly set off the news ...... the friend shared the sequence for our analysis, and when I
analysed it, it was indeed the same virus! The first subconscious thought was 'this virus is contagious'!"
Li Wenliang and others lifted the lid, and the story of the gene company's sequencing of this pathogen intersected with another story of clinician
warning. While the doctors in Wuhan Central Hospital were ineffective in their routine treatments for the emerging viral pneumonia patients and
hoped to seek answers through gene sequencing companies, Zhang Jixian, director of the Department of Respiratory and Critical Care Medicine
of Hubei Xinhua Hospital, which is adjacent to the South China Seafood Market, on December 26 On December 27, Zhang Jixian reported four
cases of "unknown viral pneumonia" to the hospital, and the hospital reported it to the Jianghan District Centre for Disease Control and Prevention
On December 28-29, Xinhua Hospital admitted three more patients from the South China Seafood Market, who had similar symptoms of viral
pneumonia. According to later reports such as the Wuhan Evening News, at 1 p.m. on December 29, Xinhua Hospital Vice President Xia
Wenguang called ten experts to discuss the seven cases, and the experts agreed that the situation was unusual and Xia Wenguang reported the
case directly to the Disease Control Division of the provincial and municipal health committees. Also reported to on the same day was the Public
Health Department of Wuhan Central Hospital. In the afternoon of the same day, Hubei Province, Wuhan City Health Commission CDC notified
the provincial, municipal and district level CDC that Xinhua Hospital and the Downtown Hospital Houhu Hospital had admitted a number of
patients with unknown pneumonia with a history of exposure to the seafood market, which triggered the start of an emergency response.
The Hubei Province CDC, the Wuhan CDC in conjunction with Jianghan District, Qiaokou District, East and the West Lake District CDCs, all
began an epidemiological investigation. Wuhan Jinyintan Hospital Vice President of Operations Huang Chaolin and others came to Xinhua
Hospital, picking up six patients. Wuhan Tongji Hospital also transferred the aforementioned first patient from the downtown hospital to Jinyintan
Hospital to do genetic testing.
On December 30, the tertiary CDC produced the "Report on the investigation and disposition of the situation of multiple cases of pneumonia in the
South China seafood market reported by hospitals". On the same day, the Wuhan Municipal Health Commission issued an internal notice,
mentioning that at a number of medical institutions in Wuhan multiple cases of unexplained pneumonia, associated with the Wuhan South China
Seafood Wholesale Market, appeared one after the other on. And it required medical institutions to report patients with similar characteristics of
unexplained pneumonia seen in the past week.
This "Urgent Notice on the Treatment of Pneumonia of Unknown Origin" by the Wuhan Health Care Commission, which was triggered by Zhang
Jixian's insistence on reporting, was soon to be found online, along with a WeChat alert from doctors such as Li Wenliang who saw the gene
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.39/54
sequencing report, allowing information about the outbreak that started in Wuhan to reach the outside world for the first time.
A warning from Shanghai
Another case sample from Wuhan Central Hospital came from the Houhu hospital area, also adjacent to the South China Seafood Market, and
was admitted a day earlier. The patient, also surnamed Chen, is a 41-year-old self-employed seafood market operator from Quanzhou, Fujian
Province, who developed a high fever of 40°C, general aching and weakness, coughing and pus, chest tightness and shortness of breath after
suffering a cold on December 20, and was admitted to Wuhan Central Hospital Houhu Hospital on December 26 with "fever investigation and lung
infection", and on December 30 The hospital took a bronchoscopic sample and left an extra copy of the respiratory lavage fluid sample in the
refrigerator at -80°C for storage.
"The reason for keeping an extra sample is that we have been cooperating with the Shanghai Public Health Clinical Centre affiliated with Fudan
University (hereinafter referred to as Shanghai Public Health Centre) and Wuhan CDC on a major national science and technology project,
'China's major natural epidemic virus resources'. Wuhan CDC is responsible for the collection of clinical samples and environmental specimens in
the Central China region, which are regularly sent to the Shanghai Public Health Centre for pathogen testing, and they have a biosafety level 3
(BSL-3) laboratory with high-throughput sequencing and bioinformatics analysis platform, while hospitals like ours are sentinel hospitals of the
Wuhan CDC." Professor Zhao Su, Department of Respiratory Medicine, Wuhan Central Hospital, introduced.
On the afternoon of December 30, the samples were taken by a chief physician of the Wuhan Centre for Disease Control and Prevention (CDC)21.
On Jan. 2, another researcher at the Wuhan CDC wrapped the samples heavily in dry ice, iron boxes and foam boxes and sent them, along with
other animal specimens, by rail express to Shanghai. On Jan. 3, Professor Zhang Yongzhen's team at the Shanghai Public Health Clinical Centre
received the samples. This centre belongs to Fudan University, Zhang Yongzhen himself is a researcher at the Institute of Infectious Disease
Prevention and Control of the Chinese Centre for Disease Control and Prevention (CDC), and adjunct professor at the Institute of Biomedical
Research of Fudan University and the Shanghai Public Health Centre. He has been engaged in scientific research work on human-animal
infectious diseases and the investigation of major natural epidemic viral foci in China in recent years under the funding of the National Natural
Foundation of China, national major special projects and national key research and development programs. Many hospitals, including Wuhan
Central Hospital, Wuhan Centre for Disease Control and Prevention (CDC), and the University of Sydney, Australia, etc, are members of the
In the early morning of January 5, Zhang Yongzhen's research team detected a novel SARS-like coronavirus from the sample and obtained the
whole genome sequence of the virus through high-throughput sequencing; the evolutionary tree drawn from the sequencing data also confirmed
that the novel coronavirus in Wuhan had never been seen before in history. The Shanghai Public Health Centre immediately reported to the
Shanghai Municipal Health and Wellness Commission and the National Health and Wellness Commission and other authorities that day, alerting
them that the new virus was homologous with SARS and should be transmitted via the respiratory tract, and suggesting appropriate disease
control and epidemic prevention measures in public places. On January 6, the CDC initiated a Level 2 emergency response internally.
"We have been working with the Wuhan CDC and Wuhan Central Hospital to collect new viruses of natural epidemic origin, which is part of our
major national project, including the use of the P3 laboratory, which is also accredited by the China National Accreditation Service for Conformity
Assessment." A researcher at the Shanghai Public Health Centre told Caixin, "We are in routine scientific research, and when we find it by
chance, the matter is so important that we immediately report it."
At least nine samples collected late last year for testing
The Caixin reporter confirmed that several other gene sequencing companies obtained samples of unidentified pneumonia cases from Wuhan
Hospital almost around the same time as Guangzhou Weiyuan Gene Technology Co. and Beijing Boao Medical Laboratory. This includes the
industry's "leader", BGI, which received a gene sequencing commission from a local hospital in Wuhan on Dec. 26, 2019. On Dec. 29, the gene
sequencing results completed by BGI on the case sample showed that the virus had 80% gene sequence similarity to SARS, but was not SARS,
but a previously unavailable coronavirus. BGI also tested the case with their SARS test kit and the results were negative, denying that it was
A BGI source told Caixin that when they sequenced samples from cases of unexplained viral pneumonia in late December, they were unaware
that the virus had clinically infected many people and had even caused aggregated infections in the same family.
"We are a technology company that does genetic sequencing, and we receive many sequencing commissions every day, and we are exposed to a
large number of viruses, and we find many new viruses. The company is a genetic sequencing technology company that receives many
sequencing commissions every day and is exposed to a large number of viruses, and also discovers many new viruses. There are many kinds of
coronaviruses, including SARS, and there are only six coronaviruses associated with people, and the only ones that are more infectious to people
are SARS and MERS. At that time we did not know whether this virus was 'good' or 'bad'. "
BGI has been cooperating with local hospitals in Wuhan for many years. According to a Caixin reporter’s investigation, local hospitals in Wuhan
sent at least 30 samples of difficult pneumonia cases to BGI for sequencing in December 2019. BGI found a total of three cases of pneumonia
caused by new coronavirus infection. Except for the case on December 26, the other two cases were collected on December 29 and 30
respectively. They mixed three SARS-like coronaviruses, that is, combined the three viral gene sequence fragments together to form a mixed viral
gene sequence. On January 1, the test reports of the three samples were reported to the Wuhan Municipal Health Commission. On January 3,
BGI conducted a high-depth full-gene sequence sequencing of the viruses in the three samples.
Caixin reporters found that as of January 19, 2020, a total of 13 samples of the new coronavirus genome sequence had been uploaded on the
GISAID platform. Except for the three articles from Japan and Thailand, the remaining 10 articles were all uploaded by Chinese scientific research
institutions. Judging from the time of sample collection, the earliest is the aforementioned case collected on December 24, 2019 and uploaded by
the Institute of Pathogen Biology of the Chinese Academy of Medical Sciences.
Eight other samples were collected on December 30, from Wuhan Jinyintan Hospital and Hubei Provincial CDC (1 entry), Jinyintan Hospital and
Institute of Virology Research, Chinese Academy of Sciences (5 entries), and the Institute of Prevention and Control of Viral Diseases, China CDC
(2 entries). In addition, the Institute for Prevention and Control of Viral Diseases of the Chinese CDC uploaded a gene sequence for samples
completed for collection on January 1, 2020.
Corroborating with this, according to Hubei Daily, on the day of December 30, Jinyintan Hospital President Zhang Dingyu led the collection of
bronchoalveolar lavage fluid from the first seven patients admitted to the hospital and sent it to the Wuhan Institute of Virology, Chinese Academy
of Sciences for testing.
Based on the industry's average detection cycle of three days, by around January 2, the gene sequencing results of the above-mentioned eight
samples collected on December 30 should have been obtained. The Wuhan Institute of Virology of the Chinese Academy of Sciences said in an
21 DRASTIC note: Disinfection of the market started on the 30th December evening (after market hours). Possibly animal samples were then taken that day, if not
then the following days. This passage suggests that some animal samples from the market were then sent to Shanghai on the 2nd Jan.
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open letter "Wuhan Institute of Virology Fully Launches Scientific Research on New Coronary Virus Pneumonia" that the Institute of Virology
received an unidentified pneumonia sample from Jinyintan Hospital on the evening of December 30. The complete genome sequence of the new
coronavirus was determined on January 2, and uploaded to GISAID on January 11.
The aforementioned paper published in the Chinese Medical Journal (English version) also showed that alveolar lavage fluid samples from five
patients were collected and sent for testing and analysis during the nine-day period from December 24, 2019 to January 1, 2020, and that two of
these five patients had no history of exposure to the South China Seafood Market.
Of the five patients, in addition to the 65-year-old patient sample mentioned above, three other patients had samples collected on December 30,
2019. Of these, patient #2 was a 49-year-old female working at the South China Seafood Market who began having a high fever and dry cough on
December 22, developed respiratory distress and was hospitalised five days later, and was admitted to the ICU on December 29; patient #3 was
also a female, 52 years old, who developed a fever on December 22 and was hospitalised on December 29, but she had no history of seafood
market exposure; patient #4 was a 41-year-old male who on December 16 He began to have a high fever and dry cough and was hospitalised on
the 22nd - this male, who also had no history of seafood market exposure, was apparently the Wuchang accountant seen above at Wuhan Central
Hospital; patient #5, whose alveolar lavage fluid sample was collected on January 1, 2020, was a 61-year-old male who worked at the South
China Seafood Market and who himself had chronic liver disease and abdominal mucinous tumour, was admitted to a local hospital after seven
days of fever, cough, and respiratory distress, and began resuscitation using ECMO on January 2 before succumbing.
According to the paper, a novel coronavirus was thus identified in the laboratory with 79% nucleotide sequence similarity to the SARS virus, which
is phylogenetically closest to the SARS-like coronavirus carried by bats, but forms a separate evolutionary branch of the coronavirus beta genus
strain sequence. After conducting virus isolation for morphological confirmation and serological testing, the new pathogen was finally confirmed to
be a novel coronavirus. The structural domain of this virus that binds to the receptor has an amino acid sequence similar to that of the SARS
coronavirus, suggesting that both viruses may bind to the same receptor on human cells.
Looking back at those few days from the end of December 2019 to the beginning of January this year, it should have been a critical moment to
decide the fate of countless people. But at that time, the public was still unaware of the consequences that the virus would later trigger.
A gene sequencing company source revealed that on January 1, 2020, he received a phone call from an official of the Hubei Provincial Health
Commission, informing him that if there were samples of cases of new crown pneumonia in Wuhan to be sent for testing, they could not be tested
again; samples of existing cases had to be destroyed, no information about the samples could be disclosed to the public, no relevant papers or
relevant data could be released to the public, and "if you detect it at a later date, you must report it to us."
On January 3, the General Office of the National Health Commission issued a notice titled "Notice on Strengthening the Management of Biological
Sample Resources and Related Scientific Research Activities in the Prevention and Control of Major Emerging Infectious Diseases," this National
Health Office Science and Education Letter (2020) No. 3 document said that for the recent Wuhan pneumonia case samples, based on the
currently available information such as etiological characteristics, transmissibility, pathogenicity, clinical data, etc., until the pathogen information is
further clarified, it is temporarily classified as highly pathogenic pathogenic microorganisms. (Class II).
The transport of samples should be in accordance with the former Ministry of Health "infectious human highly pathogenic microorganisms strains
(viruses) or samples transport management regulations"; pathogen-related experimental activities should be carried out in biosafety laboratories
with the appropriate level of protection.
Document No. 3 further stipulates that (i) all relevant institutions should provide biological samples to designated pathogen detection institutions
for pathogenic testing and proper handover procedures in accordance with the requirements of the administrative departments of health at the
provincial level or above; (ii) without approval, biological samples and their related information shall not be provided to other institutions and
individuals; institutions and individuals who have obtained biological samples of relevant cases from relevant medical and health institutions shall
immediately destroy the samples in situ or send them to the state-designated preservation institution for safekeeping, and properly keep records of
relevant experimental activities and experiments, (iii) during the period of epidemic prevention and control, the information generated by various
institutions undertaking pathogenic testing tasks is a special public resource, and no institution or individual may release information about
pathogenic testing or experimental results without permission.
As for which institutions belong to the "designated pathogen detection institutions", the document does not mention it. Virologists revealed that
even the Wuhan Institute of Virology of the Chinese Academy of Sciences was once asked to stop pathogen testing, and to destroy existing
samples, "Because according to the current ‘Law on the Prevention and Control of Infectious Diseases’, laboratory testing, diagnosis and
etiological identification of infectious diseases are the statutory duties of disease prevention and control institutions at all levels, and only national
and provincial disease control system (CDC) institutions have the right to carry out pathogenic identification of infectious diseases. The Wuhan
Institute of Virology of the Chinese Academy of Sciences is clearly not among them, not to mention those unauthorised commercial research
Perhaps because of this, the Wuhan Institute of Virology of the Chinese Academy of Sciences, which got the virus sample on December 30,
carried out virus isolation on January 1, 2020, completed the gene sequencing of the virus on January 2, and isolated the virus strain on January
5. On Jan 9, the storage and standardised preservation in the National Virus Resource Bank was completed. These research works, which can
obviously be completed around the clock, were not announced to the public for a long time. Only in February when they faced rumours and
criticism from the outside world, they gave a few words of disclosure.
On January 9, CCTV reported that the "Wuhan Viral Pneumonia Pathogen Test Results Preliminary Evaluation Expert Group" led by the China
CDC determined that the pathogen was a new type of coronavirus. "As of 21:00 on January 7, 2020, a new type of coronavirus was detected in
the laboratory, and the whole genome sequence of the virus was obtained. A total of 15 positive results of the new type of coronavirus were
detected by the nucleic acid detection method. The virus was isolated from the sample of one positive patient, and the electron microscope
showed a typical coronavirus form."
On January 11, Zhang Yongzhen's research team shared the virus genome sequence information on Virologic.org and GenBank, the first team in
the world to publish the virus sequence.
Later that day, the National Health Commission announced that China would share the genetic sequence of the new coronavirus with the WHO.
The next day, five other viral genome sequences from different patients were released on GISAID, the Global Shared Influenza Virus Database, by
a team led by the National Health and Wellness Commission. Which organisation did this share the new coronavirus gene sequence information
with the WHO? Gao Fu, director of the Chinese CDC, responded to the Caixin reporter, saying that the gene sequence came from three
institutions, the Chinese CDC, the Chinese Academy of Medical Sciences and the Chinese Academy of Sciences, and this is a joint research. The
WHO said it has obtained more detailed information about Wuhan unexplained viral pneumonia from China's National Health Commission,
including information on the gene sequence of the novel coronavirus detected from the case, which is important for other countries to develop
specific diagnostic tools.
At this point it is not really necessary to go into detail about who was the first to pick the pearl in the scientific crown, as 15 days have passed
since the first case of genetic sequencing identified the new coronavirus.
On January 11, the Wuhan Health Commission, which had stopped providing updates for several days, changed the name of "viral pneumonia of
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.41/54
unknown origin" to "new coronavirus pneumonia infection" for the first time, saying that as of 24:00 on January 10, 2020, 41 cases of new
coronary pneumonia were initially diagnosed. On the same day, the "two sessions" of Hubei were held. Until the end of Hubei's "two sessions" on
January 17, this number of cases did not increase.
Caixin reporter Zhao Jinzhao and intern reporter Huang Yuxin also contributed to this article.
#2. Caixin blog entry (Chinese, half-size) published on the 27th Feb 2020 @17:04:
This is basically a half-sized version of the full article (#1). A link at the bottom points to the new deleted full article:
#3. Short article (English) of the 3rd March 2020:
This is a considerably simplified English version of the main article, reworked with Flynn Murphy, Han Wei and Timmy Shen, and with a new title
(‘In Depth: How early coronavirus signs were spotted and throttled’). This short version in English is still available via asia.nikkei.com.
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Annexe 2 - About Vision Medicals:
Vision Medicals is the English name for 微远基因 科技有限公司 进行 (Weiyuan Gene Technology Co., Ltd).
It was set up in Guangzhou (广州)in June 2018 and still very much a start-up in Dec 2019.
The CEO of Vision Medicals is Li Yongjun, who used to work as was a bioinformatics analyst for the Institute of Pathogen Biology (Chinese
Academy of Medical Sciences), whose immediate superior, the president of the Chinese Academy of Medical Sciences, is academician Wang
Chen, also vice president of the Chinese Academy of Engineering.
Vision Medicals was involved in the sequencing of the Beijing plague cases in Nov 2019 and in the sequencing of the Guangxi pangolins in Q1
2020 (see Nature article). Incidentally Little Mountain Dog wrote a Weixin post about the Pangolins sequences where she correctly noticed that
some sequences were identical across the papers.
Vision Medicals Vision appears in the Chinese Medical Journal paper sent for publication on the 27 Jan 2030 (published May 2020) introducing
the discovery of SARS-CoV-2, with CTO Dr. Xu Teng as the co-first author of the article, Li Yongjun and Wang Xiaorui as the signed authors.
Vision Medicals is correctly listed in the contacts for the very first SARS-CoV-2 sequence (WH-01, also CNBC):
In March 2020, Vision Medicals received the CE-IVD mark for its SARS-CoV-2 Clinical Sequencing assay, which uses next-generation
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Annexe 3 - About 小山狗 (Little Mountain Dog) [true identity withheld]:
小山狗 = Xiǎoshān Gǒu, is a nickname for an employee of Vision Medicals (广州 微远基因 科技有限公司, Chinese: Guangzhou Weiyuan Gene
Technology Co., Ltd).
She was most likely born in the early 1990s, is very cultured and sensitive and a film lover.
- 2015 or earlier - 2018: Masters in Microbiology at Sun Yat-sen University, Guangzhou
- 2018 or 2019: Joins Vision Medicals, Guangzhou, China, after a possible short stint at a local competitor (maybe for an internship)
- 2022: Still at vision Medicals
For a list of Weixin articles by Little Mountain Dog see:
In particular the Timeline post is interesting.
小山狗 uses a little dog as his Weixin icon (see for instance https://freewechat.com/profile/MzAxMjMyMDk0Ng==).
小山狗 cut her handle from all the post pictures in in Document 1. This is what they should look like.
小山狗 (Little Mountain Dog)
Weixin ID: Winjor001
About Feature: 小山狗的秘密基地 (Little Mountain Dog's Secret Base)
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Annexe 4 - Timeline:
Caixin original article was supplemented by a great timeline (now deleted) that Little Mountain Dog reproduced in a blog. That timelines focussed
on the early cases, the earliest sequencings and the role of the authorities at that time. She also added a shorter timeline from Southern
Metropolis Daily (the heir of the great investigative Southern Weekly), based in Guangzhou.
Here is a more general timeline:
Timeline by email@example.com (DRASTIC)
end Nov 2019
According to multiple detailed reports never denied, at the end of Nov 19, the DIA - which mandate includes defence
diplomacy - alerts NATO and the IDF of a concerning disease with new characteristics spreading in Wuhan. That alert
is based on intelligence data points accumulating since the 2nd week of November. A formal assessment for larger
consumption across the government and its agencies (an ‘intelligence product’) will be written in December.
30 Nov 2019
According to official Chinese documents leaked to the South China Morning Post, using data compiled before the 13th
March 2020, at least 9people have already fallen ill with what will be known as Covid-19 (confirmed cases): 4 men
and 5 women, aged 39 to 79. First onset date amongst these 9 is 17th Nov.
15 Dec 2019
Ian Lipkin, professor of epidemiology at Columbia University, learns of a weird outbreak going on in Wuhan, in a
conversation with Lu Jiahai, the Director of One Health Research Center of the School of Public Health at Sun
Yat-Sen University (Guangzhou).
15 Dec 2019
According to the South China Morning Post leak (see 30 Nov 2019), using data compiled before the 13th March 2020,
there were at least 27 confirmed cases with onset date to the 15th Dec. Please note that not all of them would have
sought treatment by that time, and/or been recognized as having atypical pneumonia.
24 Dec 2019
Foreign students in one of Wuhan universities start taking precautions when moving around the city as they have
heard of a particularly bad pneumonia outbreak developing in Wuhan, in the wake of what first seemed like a fierce
but seasonal pneumonia outbreak in November.
25 Dec 2019
In an article in Freezing Point22 published the following month, investigative journalist Wang Jiaxing (himself a native
of Wuhan who went back to his city on the 18th Jan to report on the outbreak), quotes Dr Lu Xiaohong (吕小红),
Director in the Department of Gastroenterology, Wuhan Fifth Hospital:
“On December 25, 2019, I heard that medical staff in two hospitals in Wuhan were suspected of contracting viral
pneumonia of unknown cause and were quarantined, including medical staff from the respiratory department. I
realised then that the situation might not be easy.”
This shows that medical staff had already been infected by patients, and consequently isolated by the 25th Dec, which
should have provided ample proof of human to human infection. Incidentally exactly 2 health care workers infections
in 2 hospitals will be later acknowledged for 2019, with diagnosis supposedly 60 days after late Dec onset dates.
According to a WeChat post of 28th Jan 20 which was deleted within a few days by the author but fortunately saved
and still available on sina.cn,Vision Medicals (Huangpu, Guangzhou) tested sample from a patent taken on 24th Dec
and found that it was a Bat coronavirus on the 26th Dec. After having sequenced most of the virus on the 27th, they
immediately called the Central Hospital of Wuhan (which sent them the sample) on the 27th to inform them that it
was a new coronavirus.
Company executives then paid a visit to Wuhan to discuss their findings with local hospital officials and disease
control authorities and informed the CDC and Chinese Academy of Sciences.
From the WeChat post: "On the 27th and 28th, the leaders of the company also communicated with the hospital and
the CDC on the phone. On the 29th and 30th, they also went to Wuhan to report this matter in person with the leaders
of the hospital and the CDC, including all our analysis results, and with the Institute of Pathogen Biology of the
Academy of Medical Sciences. Everything is under intense, confidential, and rigorous investigation (at this time,
the hospital and disease control people already knew that there were many similar patients, and after we
communicated the test results, emergency treatment was started, but I didn't know it)." The story was confirmed by
Caixin who also checked with a doctor at the Wuhan Central Hospital.
On the 27th Dec 19, the Vision Medicals people who were analysing the new coronavirus were discussing the
possibility of a lab accident with an 'artificial' virus:
"It was also suspected that some artificial virus-related staff were inadvertently infected by accident. After all, the
community infection of Brucella some time ago was caused by the incomplete sterilisation of a certain factory
(abbreviated 'Bru' in the original WeChat post)"
27 Dec 2019
Zhang Jixian, director of the Department of Respiratory and Critical Care Medicine at Hubei Provincial Hospital of
Integrated Traditional Chinese and Western Medicine found that the chest CT films of a couple and their son showed
completely different changes from other viral pneumonias, thinking: "Generally, three people will not get the same
disease at the same time, unless it is an infectious disease. ." She reported the situation to the hospital leadership
and relevant departments.
29 Dec 2019
Epidemiological investigation begins in Wuhan
22 Freezing Point is well known for its occasional positions - in 2006 it was sanctioned for the publication of a key piece on the Boxer Rebellion by Yuan Weishi of
Sun Yat-sen University. It was relaunched within a few months but without his star editor, Li Datong, who later would be known for his opposition to constitutional
derives in China.
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30 Dec 2019
After noticing at around 5:30pm a message from Ai Fen (the head of the EA department of the hospital where he
works as an ophthalmologist) reposted by some colleagues, at around 5.42pm Li Wenliang posts a message on his
Weibo medical graduates group of about 150 members (2004 Wuhan University Clinical Class)about 7 patients at
the hospital with a pulmonary infection which returned positive tests for SARS virus. At 6:42pm Li Wenliang posts a
new message where is careful to (1) make it clear that the virus is not necessarily SARS and is being identified, (2)
alert his graduates group WeChat group that the previous post has been reported, (3) ask people to take precautions
in case of human-to-human transmission. The messages are quickly shared, even worldwide.
30 Dec 2020
After cases started appearing in hospitals, the Wuhan Municipal Health and Health Commission organised an expert
team to investigate and issued two departmental documents: the "Urgent Notice on Reporting the Treatment of
Unexplained Pneumonia" and the "Emergency Notice on Doing a Good job in the Treatment of Unexplained
Pneumonia". The two notices were shared on the Internet at 15:22 and 19:00 respectively. These documents
required respectively to conduct a comprehensive search and retrospective investigation of pneumonia cases related
to the South China Seafood Market (by returning a case declaration form by 4pm the same day) and to organise a
strong structured effort to handle the situation.
The second notice also prevented the release of treatment information without authorization. See link for instance.
30 Dec 2020
Light disinfection of some stalls' metal curtains in the evening (when the stalls are closed after market hours).
That disinfection may actually be routine - it happened several times a week, after closure (around 6 to 7pm).
More (non-routine) disinfection of public space (not the inside of stalls) happened the following day in the early
morning (~2am), and then in the morning while the market was open.
31 Dec 2019
The outbreak becomes known worldwide as Mr Chen's case file and indication of a SARS-like infection hits social
media, largely due to the postings of Ai Fen and Li Wenliang from the Wuhan central hospital the day before (30th
After receiving a call at 1:30am on the 31st, Li Wenliang spent 2 hours at the Wuhan Municipal Health Commission
where he was asked about his source before being able to go back home at 4am.
31 Dec 2019
At 13:38 the Wuhan Municipal Health and Health Commission issued the "Circular on the Current Pneumonia
Epidemic in Our City", stating that 27 cases have been found and that "so far, no obvious human-to-human
transmission has been found in the investigation, and no medical staff infection has been found." (see also Caixin).
31 Dec 2019
China notifies the World Health Organisation (WHO) about the emergence of an unidentified infectious disease.
China CDC experts arrived to launch a three-level joint task force. It was agreed that the identified cases were
pneumonia of unknown aetiology. (see China-WHO report Annexe D4).
Hubei provincial officials, and experts from the main China CDC in Beijing were all in Wuhan working together on the
31 Dec 2019
According to the South China Morning Post leak (see 30 Nov 2019), using data compiled before the 13th Mar 2020,
there were in total at 266 confirmed cases with onset date in 2019.
1 Jan 2020
The Huanan Seafood market is closed. at 8am. See also Beijing News.
First environmental samples are collected.
1 Jan 2020
A first team of experts from the National Health and Health Commission arrived in Wuhan in the morning.
1 Jan 2020
According to the South China Morning Post leak (see 30 Nov 2019), using data compiled before the 13th March 2020,
there were in total at 381 confirmed cases with onset date up to Jan 1st, a jump of 115 from the previous day.
1 Jan 2020
BGI tested samples received on Dec 26 (x1) and Dec 29 (x2) and reports the results to the Wuhan Municipal Health
Commission on the 1st Jan 2020.
1 Jan 2020
After several batches of genome sequence results had been returned to hospitals and submitted to health authorities,
an employee of one genomics company received a phone call from an official at the Hubei Provincial Health
Commission, ordering the company to stop testing samples from Wuhan related to the new disease and destroy all
existing samples. They were told to immediately cease releasing test results and information about the tests, and
report any future results to authorities.
According to Caixin this happened at all gene sequencing companies in Wuhan (and likely not in other parts of China,
like Shanghai). This also happened at the WIV.
2 Jan 2020
Wuhan Central Hospital requires medical staff not to discuss the condition publicly, especially through text and
pictures, and the condition can only be mentioned orally during shifts.
At the same time, due to administrative intervention, the hospital almost stopped "direct online reporting"
2 Jan 2020
The Wuhan Institute of Virology fully sequences SARS-CoV-2 after it received a sample from Jinyintan Hospital the
30th Dec 2019 and isolated the virus strain on the 5th Jan.
3 Jan 2020
The National Health Commission, China’s top medical authority, issued its own gagging order. Laboratories were
told not to release any information and to hand over or destroy the sample.
3 Jan 2020
The Wuhan Municipal Public Security Bureau admonished 8 doctors who spread information about the epidemic
on the Internet (including Li Wenliang, Xie Linka and Liu Wen), and publicised it through CCTV and other public
3 Jan 2020
As a result of the initial observation in a few key hospitals of an epi-link with this seafood market, the initial case
definition included an epi-link to the market in the Wuhan issued (Green book)
Professor Zhang Xiaochun of the Department of Imaging, Zhongnan Hospital of Wuhan University, publicly
questioned the reliability of nucleic acid detection for diagnosing new coronary pneumonia, and suggested that CT
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images should be used as the main basis for diagnosis.
This won't be done before the 5th Feb.
3 Jan 2020
China answers an official request for information from the WHO (posted 1st Jan) within the required 2-day window.
3 Jan 2020
Professor Zhang Yongzhen of Fudan University in Shanghai received biological samples packed in dry ice in metal
boxes and shipped by rail from Wuhan Central Hospital.
By January 5, Zhang’s team had also identified the new, SARS-like coronavirus by using high-throughput
sequencing. The sequence will be released to the world with pressure from Farrar and Holmes on the 10th Jan 20.
3-7 Jan 2020
On the 3rd Jan 2020, the first complete genome of the novel β genus coronaviruses (2019- nCoVs) was identified in
samples of bronchoalveolar lavage fluid (BALF) from a patient from Wuhan by scientists of the National Institute of
Viral Disease Control and Prevention in Beijing (IVDC, part of the CDC) through a combination of Sanger
sequencing, Illumina sequencing, and nanopore sequencing.
On the 7th Jan Song Jingdong (宋敬东), associate researcher and a student of Hong Tao (who was implicated in the
2004 SARS leaks at the IVDC, with 4 primary cases including 2 covered-up), takes the first electron microscope
picture of SARS-CoV-2.
Sometime in Jan 2020 or Feb 2020 an researcher gets infected with SARS_CoV-2 during lab work at the IVDC. The
case was never officially disclosed.
4 Jan 2020
The head of the University of Hong Kong's Centre for Infectious Diseases, Ho Pak-leung, warns that the city should
implement the strictest possible monitoring system for the new pneumonia, as it is highly possible that the illness is
spreading from human to human.
5 Jan 2020
The Wuhan Municipal Health Commission notified that 59 cases of diagnosed viral pneumonia were in line with
unknown causes; and re-emphasized that the preliminary investigation showed that no obvious human transmission
was found and no medical personnel were infected. [As Daszak would soon point out, it was actually difficult to
imagine how there could be 59 primary cases, all infected directly by animals].
These 59 are likely the (41 + 18) of the Lancet study, with 18 clinically diagnosed but no showing any viral load by
RT-PCR (which would have difficulties detecting any case 2 weeks after onset - the blood samples were taken
AFTER transfer to the designate hospital on 31st Dec 2019 - typically 2 to 5 days after transfer).
- Serological detection was not done to look for 2019-nCoV antibody rises in 18 patients with undetectable viral RNA.
kinetics of viral load and antibody titres were not available.
- 59 suspected cases with fever and dry cough were transferred to a designated hospital (Jin Yin-tan Hospital )
starting from Dec 31, 2019 (59-18=41).
5 Jan 2020
The Jianghan District Center for Disease Control and Prevention required the completion of hospital and district
consultations before reporting;
The Health Committee requires that the report can only be reported after the approval of the provincial and municipal
health and health committees.
5 Jan 2010
After the CDC (NIVDC) on the 3rd Jan, the WIV on the 2nd and BGI and Vision Medicals respectively on the 30th and
27th Dec, the Chinese of Medical Sciences (which was in contact with Vision Medicals since the 27th Dec) fully
sequenced the virus in the early hours (just after midnight).
The same day the Shanghai Public Clinical Health Center, led by famed virologist Zhang Yongzhen, was the latest to
sequence the virus.
6 Jan 2020
After Zhang reported his findings of a new coronavirus which he had just sequenced (on the 5th) to the Shanghai
Municipal Health Commission as well as China’s National Health Commission, warning the new virus was like
SARS, and was being transmitted through the respiratory route. This sparked a secondary emergency response
within the Chinese Centre for Disease Control and Prevention (CDC) on January 6.
6-17 Jan 2020
"Two sessions" (两会) of Wuhan City and Hubei Province were held successively.
6-17 Jan 2020
No new cases are published by the Center for Disease Control or the Wuhan Health Commission.
7 Jan 2020
In an speech at the Politburo Standing Committee made on the 3rd Feb 2020 (and released on the 15th Feb 2020),
Mr. Xi mentioned he had “issued demands about the efforts to prevent and control” the coronavirus on the 7th Jan
2020, during a previous meeting of the Politburo Standing Committee, the highest council of the Communist Party,
whose sessions are typically cloaked in secrecy.
We should not overdo the session of the Standing Committee of the CPC Central Political Bureau on 7th Jan when Xi
Jinping made a request to "to do a good job in epidemic prevention and control." This was just two days after the
second-level emergency response was launched within the National Center for Disease Control and Prevention
(National CDC). The report of the meeting actually does not mention epidemic prevention and control, according to
this source: https://2newcenturynet.blogspot.com/2020/03/blog-post_3.html.
Most likely Xi Jinping just mentioned it, but quite possibly with the hope that it could be dealt with quickly and not
disturb the Chinese New Year. So effectively it was mentioned just to be better dismissed by Chinese New Year. Not
a priority at the time.
8 Jan 2020
The Wall Street Journal embarasses China and the WHO by reporting that scientists had identified a new coronavirus
in samples from pneumonia patients in Wuhan, while still no official news is yet released by China. Behind the scene
the Chinese CDC was allegedly positioned to write the first paper announcing while all other labs were bound by the
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The next day international pressure starts building up on China.
8-18 Jan 2020
The second group of experts from the National Health Commission arrived in Wuhan, after the first group of experts
made their way to Wuhan on the morning of the 31st Dec 19.
During the period from January 8 to 18, 2020, when the second group of experts was working in Wuhan, almost all
relevant departments of the medical system in Wuhan were aware of the fact that medical staff were infected and
"human-to-human" transmission occurred, but no one reported to the expert group.
9 Jan 2020
The "Wuhan Viral Pneumonia Pathogen Preliminary Evaluation Expert Group" , an expert team led by the CDC,
made a preliminary conclusion that the disease was caused by a new strain of coronavirus, according to Chinese
state broadcaster CCTV.
Xu Jianguo (徐建国), of the Chinese Academy of Engineering, and leader of the expert team tasked with evaluating
test results on the Wuhan pneumonia, said on January 9 that that the preliminary conclusion they have arrived at was
that the pathogen that had infected several people in Wuhan took the form of a coronavirus.
Chinese media start mentioning the outbreak.
10 Jan 2020
The Chinese Center for Disease Control and Prevention developed a diagnostic kit. The new coronavirus pneumonia
virus can be detected by the kit and RT-PCR technology, so the "confirmed case" standard was added, requiring
"positive virus test".
However getting test kits was really difficult and they had a high false negative rate.
10 Jan 2020
Science published an article announcing the findings of the Expert Group of the previous day.
At the same time the article raises doubt as to the absence of human-to-human transmission, given the high number
of cases recorded so far (at least 59). quoting Daszak:
"I don't understand how you can get so many cases without human-to-human transmission," Daszak says. "This is
something I have a red flag on."
11 Jan 2020
The Wuhan Municipal Health Commission reduces the number of cases from 59 to 41.23
59 was 41 confirmed by RT-PCR + 18 suspected but without viral load.
Basically the suspected are not included any more - which may reject perfectly valid cases which were simply tested
with RT-PCR 2 weeks plus after onset when viral load becomes difficult to detect.
Chinese authorities justified this by saying that genomic test kits rejected all these 18.
The update from the National Health Commission (NHC) reiterated that 'There have been no new cases since
January 3. For the time being, the Mainland's investigation has neither identified any infection of healthcare workers
nor definite evidence of human-to-human transmission'.
11 Jan 2020
Farrar and Holmes force the release of the virus sequence to the world.
13 Jan 2020
First case outside China, in Thailand, raising the likelihood of human transmission for international observers.
14 Jan 2020
The head of China’s National Health Commission, Ma Xiaowei, laid out a grim assessment of the situation on Jan. 14
in a confidential teleconference with provincial health officials. A memo states that the teleconference was held to
convey instructions on the coronavirus from President Xi Jinping, Premier Li Keqiang and Vice Premier Sun Chunlan,
but does not specify what those instructions were. “The epidemic situation is still severe and complex, the most
severe challenge since SARS in 2003, and is likely to develop into a major public health event,” the memo cites Ma
as saying. Under a section titled “sober understanding of the situation,” the memo said that “clustered cases suggest
that human-to-human transmission is possible.” It singled out the case in Thailand, saying that the situation had
“changed significantly” because of the possible spread of the virus abroad.
See also https://www.cnbc.com/2020/04/15/china-didnt-warn-public-of-likely-pandemic-for-6-key-days.html
15 Jan 2020
Now two weeks have passed since the closure of the market. Any new case must be due to human-to-human
infection due to max 2 weeks incubation period (estimated at the time).
“We have reached the latest understanding that the risk of sustained human-to-human transmission is low,” Li Qun,
the head of the China CDC’s emergency center, told Chinese state television on Jan. 15. That was the same day Li
was appointed leader of a group preparing emergency plans for the level one response, a CDC notice shows.
15 Jan 2020
500 hospital staff had been confirmed infected by mid-January, with a further 600 suspected, according to multiple
sources and a slide from a CDC presentation. See also this source.
16 Jan 2020
Institut Pasteur Shanghai and some Shanghai labs sent an analysis in the form of a letter to the journal 'Science
China - Life Sciences'. The analysis concludes that 'To our surprise, despite replacing four out of five important
interface amino acid residues, the Wuhan CoV S-protein was found to have a significant binding affinity to
human ACE2' and that 'The Wuhan CoV poses a significant public health risk for human transmission via the
S- protein–ACE2 binding pathway'. See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089049/.
This was before h2h transmission was properly acknowledged and while the official count of confirmed cases has not
increased since the 5th Jan (it was actually decreased on the 11th Jan. The letter is published online on the 21st Jan
16 Jan 2020
The National Health and Medical Commission released the first version of the "Diagnosis and Treatment Plan for
Novel Coronavirus Infected Pneumonia (Trial)", and the implementation of the "Trial Diagnosis and Treatment Plan"
and "Inclusion and Exclusions Standards" of the 3rd Jan with their epi-link to the market were stopped
23 See https://web.archive.org/web/*/http://wjw.wuhan.gov.cn/front/web/showDetail/202001* for the archived updates for January 2020 from the Wuhan Health
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.48/54
17 Jan 2020
On the last day of the 'two-sessions' of the party and more than two weeks after closure of the market, a total of 4
new patients were diagnosed for the first time since the 5th Jan 20.
This is the very first change up since the 5th Jan 2020 (there was a reduction from 59 to 41 on the 11th Jan).
In a release that will long be remembered, the Wuhan Municipal Health Commission stated:
”An analysis of the epidemiological data of new coronavirus-infected pneumonia cases released in the previous
period found that some cases have no history of exposure to the South China Seafood Wholesale Market. On the
basis of standardising pre-examination and triage and fever diagnosis, the optimised detection kit was used to
sample and monitor unexplained pneumonia cases isolated from fever diagnosis and treatment in the city, and 17
new coronavirus nucleic acid positive cases were detected” .
17 Jan 2020
Yuan Guoyong, a member of the high-level expert group of the National Health and Health Commission, previously
discovered a family aggregation case that returned from Wuhan to Shenzhen. One of the patients who had no history
of Wuhan travel was also tested positive, so he inferred that the new coronavirus pneumonia can spread among
people. On January 17, he notified Gao Fu, director of the Chinese Center for Disease Control and Guangdong
Center for Disease Control through a written report, and disclosed this information to other expert group members.
18 Jan 2020
On the evening of January 18, 2020, the third group of experts from the National Health Commission led by
Academician Zhong Nanshan rushed to Wuhan.
18 Jan 2020
The Wuhan health commission resumed public notices about the outbreak, announcing that in the 24 hours of
January 16, four new cases of the coronavirus had been discovered.
18 Jan 2020
Wuhan’s Baibuting district held its annual mass banquet. On the 20th anniversary of the event, the organisers
attempted to break a world record for the largest number of dishes served.
Long tables in 10 locations were laid out with a total of 13,986 dishes, some bearing patriotic names such as
Motherland in My Heart (cucumber and ham), and One Belt One Road (vegetable salad).
10,000 families were present at the banquet. At the same time Wuhan Culture and Tourism Bureau distributed
200,000 local tourist activity vouchers.
19 Jan 2020
In the early morning of January 19, Wuhan City issued a notice saying that 17 patients had been found newly infected
with the virus on January 17, raising the total number of confirmed cases to 62 (41 + 4 + 17).
This is not 1/10 of the 757 confirmed cases to Jan 10 (onset date) later published by the CDC (17th Feb).
19 Jan 2020
136 additional new cases were diagnosed as the epi-link to the market was no longer required (since 16th Jan), and
cases were subsequently found in multiple hospitals and clinics across Wuhan.
20 Jan 2020
Wuhan Culture and Tourism Bureau distributes 200,000 local tourist activity vouchers.
News of cultural tourism activities during the Spring Festival was not only on the front page of Wuhan Evening News
on January 20, but also with a news guide below "No need to wear N95 masks to general public places" (meaning
that ordinary one will do, as N95 were really needed for medical professionals).
This was the acme of the gulf between Wuhan local authorities playing the situation down and the rest of China
reporting in a much more critical way.
20 Jan 2020
For the first time, Wuhan health commission’s announcement removed previous statements that “limited
person-to-person transmission cannot be ruled out,” and that “the risk of continuous person-to-person transmission is
Wang Guangfa, a member of the expert group, proved "human-to-human transmission" with personal infection. He
became ill after returning to Beijing on January 16 and was diagnosed on January 20.
In an interview in Beijing on the same day Zhong Nanshan affirmed the "human-to-human transmission" of the new
crown pneumonia, and confirmed that medical staff were infected.
20 Jan 2020
The China CDC would retrospectively report in their ‘CDC Weekly’ publication dated 17th Feb that there had been
6,070 confirmed cases and 410+ deaths to the 20th Jan 2020.
20 Jan 2020
6 days after the internal grim assessment of the situation during a confidential teleconference, President Xi Jinping
warned the public on the 20th Jan.
20 Jan 2020
Shi Zheng-Li paper announcing the discovery of SARS-CoV-2, with sequencing and isolation at the WIV is sent for
publication in Nature. It is published on the 3rd February 2020 (
https://www.nature.com/articles/s41586-020-2012-7#article-info) but was first published as a preprint on the 23rd Jan
See also 25 Jan 2020 below
21 Jan 2020
“The 2020 Hubei Province Spring Festival troupe theatrical performance was successfully held in Wuhan Hongshan
Auditorium. The Hubei Provincial Party Committee The secretary, governor and other leaders attended the
performance together with representatives from all walks of life in the province. [---]. More than 40 performers from
Hubei Provincial National Song and Dance Troupe participated in many In the performance of this program, the
actresses overcame multiple difficulties such as long-distance running, stuffy nose, cold, and physical discomfort, and
after taking the stage, they performed with full firepower and performed perfectly when they were sick. It created a
festive, cheerful, and progressive festive atmosphere, and the performance was fully appreciated by the provincial
22 Jan 2020
The Central Committee of the Communist Party of China required Hubei Province to implement comprehensive
and strict control over the outflow of people.
23 Jan 2020
Wuhan goes into lockdown.
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25 Jan 2020
A major paper is sent for publication in the English edition of the Chinese Medical Journal. That paper goes into detail
of the careful identification and isolation of SARS-CoV-2. This critical paper was only published online on the 11th Feb
3 Feb 2020
Dr. Zhang, a radiologist at Zhongnan Hospital in central Wuhan who had served on the front lines of SARS in 2003
took to her social messaging account to call for the use of chest X-rays in diagnosing Covid-19, instead of lab tests
that were resulting in so many false negatives. She raised the alarm on cross-infection within families,
recommending the government make use of hotels and school dormitories to quarantine suspected cases.
5 Feb 2020
The National Health and Medical Commission issued the fifth edition of the New Coronary Pneumonia Diagnosis
and Treatment Plan, which stipulated that CT images should be used as clinical diagnostic criteria. Until then there
was no confirmed case based on CT despite the absence of test kits (often unreliable anyway) in the early days
11 Feb 2020
Academician Zhong Nanshan pointed out to the media: Wuhan City lost control of the virus in the early stage, and the
work was not done well. The local government and health department should bear some responsibility.
12 Feb 2020
13,332 clinically diagnosed cases were retrospectively reported from Hubei that day. This was the first time China has
reported clinically diagnosed cases in addition to laboratory-confirmed cases.
Practically that meant many more patients could have a better chance of access to treatment, including hospital beds
and quarantine locations as they opened up
14 Feb 2020
The China CDC reported in their CDC Weekly publication (published Feb 17) that there had been 104 confirmed
patients with onset of symptoms before Dec. 31. In addition, there were also 37 clinically-diagnosed patients in
December, and 25 suspected, for a grand total of 166.
This number, gathered before any in-depth retrospective search for cases and before the first WHO mission to China,
is effectively still the official number for 2019 (174 cases released in the China-WHO mission report in Feb 2021).
21 Feb 2020
The China CDC releases the Novel Coronavirus Pneumonia Prevention and Control Plan (Fifth Edition)
3 Mar 2020
As part of one of the last rounds of market decontamination, a family of 4 is found still living in the dormitory of the
market. They had been there for 43 days (so came back around the 20th Jan 2020 before the lockdown). The man in
his 60s in the family was Gu Gangsheng, a former manager of the market, and merchants usually call him "Lao Gu".
The dormitory where his family lived during the epidemic was located on the second floor of the East District of
Huanan Seafood Market. Gu had lived in the dormitory since 2012.
21 Feb 2021
As part of the China-WHO mission report (first disclosed by CNN two weeks earlier), 174 confirmed cases for Dec 19
are published. This is essentially the same number as compiled by the Chinese CDC on the 14th Feb 2020, one year
earlier and before any in-depth retrospective investigation.
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.50/54
Annexe 5 - Technical Insights (with the help of Adrian Jones):
#1. Shotgun Metagenomics
The technology used by Vision Medicals for quickly screening for pathogens is called shotgun metagenomics, and is an application of
metagenomics New Generation Sequencing (mNGS). The exact application of shotgun metagenomics developed by Vision Medicals was first
marketed as IDSeqTM around August 2019.
Here are some good articles co-authored or with contributions by Vision Medicals that explain the mNGS detection process and its place in the
● ‘mNGS in clinical microbiology laboratories: on the road to maturity’ (Oct 2019):
● ‘Multicenter assessment of shotgun metagenomics for pathogen detection’ (Oct 2021):
● ‘Development and evaluation of a rapid CRISPR-based diagnostic for COVID-19’ (Aug 20), for a comparison of mNGS, RT-PCR and
CRISPR-based diagnostics for COVID-19: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7451577/
This is the name of a contig in SPAdes convention which was thus the software used for the assembly of the raw reads
16579 is the contig length (a partial sequence of the virus obtained by automatically merging the overlapping short reads)
Cov means coverage, 266.242859 is the mean coverage (the number of reads containing the Kmer with K the last one used for filtering the Bruijn
#3. On the two sequencing runs:
"Later, in-depth analysis was carried out from the gene level (orf1ab, S, N and other genes), and there was no significant discovery, mainly
because the number of detected sequences was small, the coverage rate was too low, and they were all incomplete genes. Nothing"
“Retesting of complementary data for analysis was proposed at noon. Retesting allows for technical reproducibility validation, avoiding false
positives due to contamination by some unknown factors, ensuring that the sample does have the pathogen, and additionally allows for more data
to be analysed, such as the ability to assemble a complete genome, with more reliable analysis results and more in-depth analysis that can be
“The next day (2019.12.27), after the data came out early in the morning, the assembly analysis was carried out quickly, and a nearly
complete genome sequence was finally assembled. The data was also shared with other in-depth analyses of pathogens by the Chinese
Academy of Medical Sciences. This time, the number of reads has increased from more than 500 to more than 470,000!”
Clear indication that there was a 2nd sequencing run (during the night between 26th December and 27th December) probably on a better
machine. The first sequencing produced enough reads to indicate the presence of a new sarbecovirus but not enough to obtain a near complete
genome, in contrast to the second run that was of high quality.
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (firstname.lastname@example.org), p.51/54
Bad genome coverage in the 1st sequencing run (x-axis is the genome
coordinate, y-axis is the number of short reads mapping to it)
Very good coverage in the 2nd sequencing run
#4. Some issues with the plots
There are several pairwise similarity plots (of a fasta with 150 coronaviruses and the new sarbecovirus added). They look strange because they
are not symmetric. For some unclear reason some rows are switched (not the same ordering as the columns) moving a few rows restores the
symmetry which is what we expect for a pairwise similarity plot (image on the right produced by DRASTIC).
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.52/54
#5. Comparison to the SARS virus sequence brom Boao lab in Beijing:
We can see on the plot below that the new coronavirus obtained byVision Medicals is near identical to another called Boao_SARS [name partly
blurred on image, but only on vertical line].
This refers to Beijing Boao medical laboratory, the one that sequenced the samples from the 41 year-old accountant whose whose (incorrect)
“SARS” diagnostic leaked on wechat on the 30th Dec, becoming viral during the night as the whistle-giver (Ai Fen) and whistle blower (Li Wenliang)
That patient lived in the dense residential district closest to the WIV new site in the south of Wuhan and after he transferred to the Wuhan Central
Hospital on the other side of the river to the emergency department of Ai Fen where his uncle/aunt worked, as he was not improving in his local
As the Vision Medicals employee explains in her blog, she received that new sample in the early hours of the 30th Dec from some friend at Boao:
“In the middle of the night on the 30th, I got the sequence from a friend’s business for analysis.”
Source Caixin report https://web.archive.org/web/20200227094018/http://china.caixin.com/2020-02-26/101520972.html
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (firstname.lastname@example.org), p.53/54
#6. Inverted last contig:
In this plot the author merged the contig and plotted the identity to Bat SLCoV-ZC45 (red for higher identity) which showed that the last contig was
inverted (minus sense, reverse complement). The simplot was added by DRASTIC for comparison
Vision Medicals: SARS-CoV-2 sequencing and analysis - 26th-27th Dec 19 DRASTIC (email@example.com), p.54/54